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#1: 122 LESCH-NYHAN-SYNDROME / all subheadings
MEDLINE EXPRESS (R) 1/96-12/96 1 of 122
TI: Lesch-Nyhan syndrome and its pathogenesis: normal nicotinamide-adenine dinucleotide but reduced ATP concentrations that correlate with reduced poly(ADP-ribose) synthetase activity in HPRT-deficient lymphoblasts.
AU: McCreanor-GM; Harkness-RA
AD: Division of Inherited Metabolic Diseases, MRC Clinical Research Centre and Northwick Park Hospital, Harrow, Middlesex, London, UK.
SO: J-Inherit-Metab-Dis. 1995; 18(6): 737-47
ISSN: 0141-8955
PY: 1995
LA: ENGLISH
CP: NETHERLANDS
AB: In hypoxanthine (guanine) phosphoribosyltransferase- (HPRT; EC 2.4.2.8) deficient lymphoblasts, ATP but not nicotinamide-adenine dinucleotide coenzyme concentrations are reduced by limited nutrition. Such reduced ATP concentrations are correlated with reduced poly(ADP-ribose) synthetase (polyADPRT; EC 2.4.2.30) activity; this reduces the breakdown of nicotinamide-adenine dinucleotide coenzymes and thus explains their normal intracellular concentrations. Since reductions in poly(ADP-ribose) synthetase activity reduce DNA repair, alterations in DNA could accumulate even in non-multiplying cells such as neurons, especially in the continuously active 'respiratory centre'. Our Lesch-Nyhan patients suffered respiratory deaths between 15 and 20 years of age.
MESH: DNA-Damage; DNA-Repair; Lesch-Nyhan-Syndrome-metabolism
MESH: *Adenosine-Triphosphate-metabolism; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-etiology; *NAD-metabolism; *NAD+-ADP-Ribosyltransferase-metabolism
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.30; EC 2.4.2.8; 53-84-9; 56-65-5
NM: NAD+-ADP-Ribosyltransferase; Hypoxanthine-Phosphoribosyltransferase; NAD; Adenosine-Triphosphate
AN: 96343354
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 2 of 122
TI: Germinal HPRT splice donor site mutation results in multiple RNA splicing products in T-lymphocyte cultures.
AU: Hunter-TC; Melancon-SB; Dallaire-L; Taft-S; Skopek-TR; Albertini-RJ; O'Neill-JP
AD: University of Vermont Genetics Laboratory, Burlington, Vermont 05401, USA.
SO: Somat-Cell-Mol-Genet. 1996 Mar; 22(2): 145-50
ISSN: 0740-7750
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: We have used peripheral blood T-lymphocyte cultures to analyze the hprt mutation in two Lesch-Nyhan syndrome males who are cousins and to confirm the carrier status of female members of the family. Both cDNA and genomic DNA sequencing studies show that this patient carries a hitherto undescribed single base deletion in the exon 5 donor splice site sequence (I5: +1, delta G, base number 31635). The largest cDNA product contained all nine hprt exons plus an insertion of 66 bases of intron 5, consistent with the use of a cryptic splice site in intron 5 (aag67/gtaagc). This splicing error would result in a chain terminating codon immediately after exon 5 (I5:2-4, taa) and predicts a polypeptide of 133 amino acids. This loss of the normal splice donor site also results in multiple hprt mRNA species, combining the use of the cryptic splice site in intron 5 and splicing errors involving exons 2-6. In addition to defining a new Lesch-Nyhan mutation (hprtHenryville), these results provide insight into aberrant splicing of hprt mRNA in T-lymphocytes.
MESH: Base-Sequence; Cells,-Cultured; Child-; DNA-genetics; DNA-Mutational-Analysis; DNA,-Complementary-genetics; Exons-genetics; Heterozygote-Detection; Infant-; Molecular-Sequence-Data
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *RNA-Splicing-genetics; *Sequence-Deletion-genetics; *T-Lymphocytes
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA,-Complementary; DNA
AN: 96376386
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 3 of 122
TI: Dopamine, serotonin and tachykinin in self-injurious behavior.
AU: Sivam-SP
AD: Department of Pharmacology & Toxicology, Indiana University School of Medicine, Gary 46408, USA.
SO: Life-Sci. 1996 May 24; 58(26): 2367-75
ISSN: 0024-3205
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6-hydroxydopamine (6OHDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (approximately 30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (> 90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.
MESH: Cocaine-pharmacology; Lesch-Nyhan-Syndrome-psychology; Piperazines-pharmacology; Rats-; Self-Injurious-Behavior-chemically-induced
MESH: *Dopamine-physiology; *Self-Injurious-Behavior-etiology; *Serotonin-physiology; *Tachykinins-physiology
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: S07RR5371RRNCRR; NS26063NSNINDS
RN: 0; 0; 50-36-2; 50-67-9; 51-61-6; 67469-78-7
NM: Piperazines; Tachykinins; Cocaine; Serotonin; Dopamine; GBR-12909
AN: 96282652
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 4 of 122
TI: Mutational analysis of the human MAOA gene.
AU: Tivol-EA; Shalish-C; Schuback-DE; Hsu-YP; Breakefield-XO
AD: Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA.
SO: Am-J-Med-Genet. 1996 Feb 16; 67(1): 92-7
ISSN: 0148-7299
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The monoamine oxidases (MAO-A and MAO-B) are the enzymes primarily responsible for the degradation of amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. Wide variations in activity of these isozymes have been reported in control humans. The MAOA and MAOB genes are located next to each other in the p11.3-11.4 region of the human X chromosome. Our recent documentation of an MAO-A-deficiency state, apparently associated with impulsive aggressive behavior in males, has focused attention of genetic variations in the MAOA gene. In the present study variations in the coding sequence of the MAOA gene were evaluated by RT-PCR, SSCP, and sequencing a mRNA or genomic DNA in 40 control males with > 100-fold variations of MAO-A activity, as measured in cultured skin fibroblasts. Remarkable conservation of the coding sequence was found with only 5 polymorphisms observed. All but one of these were in the third codon position and thus did not alter the deduced amino acid sequence. The one amino acid alteration observed, lys --> arg, was neutral and should not affect the structure of the protein. This study demonstrates high conservation of coding sequence in the human MAOA gene in control males, and provides primer sets which can be used to search genomic DNA for mutations in this gene in males with neuropsychiatric conditions.
MESH: Base-Sequence; Cells,-Cultured; DNA-Mutational-Analysis; DNA-Primers; Fibroblasts-cytology; Fibroblasts-enzymology; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymorphism,-Single-Stranded-Conformational; Skin-cytology; Skin-enzymology
MESH: *Monoamine-Oxidase-genetics; *Mutation-
TG: Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: NS21921NSNINDS; MH52416MHNIMH
RN: EC 1.4.3.4; 0
NM: Monoamine-Oxidase; DNA-Primers
AN: 96233807
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 5 of 122
TI: Novel nonsense mutation in the hypoxanthine guanine phosphoribosyltransferase gene and nonrandom X-inactivation causing Lesch-Nyhan syndrome in a female patient.
AU: Aral-B; de-Saint-Basile-G; Al-Garawi-S; Kamoun-P; Ceballos-Picot-I
AD: CNRS USA 1335, Paris, France.
SO: Hum-Mutat. 1996; 7(1): 52-8
ISSN: 1059-7794
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Lesch-Nyhan (LN) disease is a severe X-linked recessive neurological disorder associated with a loss of hypoxanthine guanine phosphoribosyltransferase activity (HPRT, EC 2.4.2.8). We have studied the second example of a female patient with LN disease. The molecular basis of HPRT deficiency in this patient was a previously undescribed nucleotide substitution in exon 6. In this gene, designated HPRT PARIS, a single nucleotide substitution from T to G at base position 558 changed a tyrosine (TAT) to a codon STOP (TAG) (Y153X). Analysis of the mother revealed a normal sequence of the HPRT cDNA and demonstrated that this mutation arose through a de novo gametic event. Allele-specific amplification of exon 6 from the patient's genomic DNA confirmed the single base substitution and showed that the patient was heterozygous for this mutation. Investigation of X-chromosomal inactivation by comparison of methylation patterns of patient's DNA isolated from fibroblasts, T lymphocytes, and polymorphonuclear cells digested with PstI and BstXI, with or without HpaII, and hybridized with M27 beta probe indicated a nonrandom pattern of X-chromosomal inactivation in which there was preferential inactivation of the maternal allele. The data indicate that nonrandom X-inactivation leading to selective inactivation of the maternal gene and a de novo point mutation in the paternal gene were responsible for the lack of HPRT activity in this patient.
MESH: Amino-Acid-Sequence; Base-Sequence; Cells,-Cultured; Exons-; Fibroblasts-ultrastructure; Heterozygote-Detection; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Restriction-Mapping
MESH: *Dosage-Compensation-Genetics; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Point-Mutation
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 96263738
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 6 of 122
TI: Regulation of the hypoxanthine phosphoribosyltransferase gene: in vitro and in vivo approaches.
AU: Jiralerspong-S; Patel-PI
AD: Department of Neurology, Baylor College of Medicine, Houston, Texas 77030-3411, USA.
SO: Proc-Soc-Exp-Biol-Med. 1996 Jun; 212(2): 116-27
ISSN: 0037-9727
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The hypoxanthine phosphoribosyltransferase (HPRT) locus is a constitutively expressed housekeeping gene characterized by a notably higher level of expression in the mammalian brain. The enzyme it encodes is key to purine salvage in humans and is the basis for the X-linked recessive disorder, Lesch-Nyhan syndrome (LNS). Methylation in the promoter plays a critical, if not fully understood, role in transcriptional silencing of the locus on the inactive chromosome, possibly by conferring structural stability. In vivo footprinting assays of the promoter region have shown protein interaction with multiple Spl-binding sites, a possible AP2 site, and a potentially novel binding site. In vitro studies of HPRT promoter deletion constructs have identified a minimal promoter element necessary for maximal transcription and a position-dependent, orientation-independent repressor element (HPRT-NE) that functions on heterologous promoters. Regulatory intron elements have also been observed. Studies on transgenic mice bearing HPRT promoter constructs have shown that the minimal promoter element is insufficient for in vivo expression and that HPRT-NE is responsible for conferring neuronal specificity. HPRT-mice possess metabolic defects similar to LNS patients, but fail to develop human behavioral abnormalities, perhaps because of species differences in purine metabolism. A neuronal-specific protein complex appears to be necessary for activator function of HPRT-NE, while a ubiquitously expressed complex may be responsible for repression. Sequence analysis Indicates that the latter complex may depend on the multifunctional transcription factor YY1 for binding. A fuller understanding of HPRT gene regulation will hopefully provide insight into the transcriptional mechanisms controlling the expression of housekeeping and brain-specific genes.
MESH: Arthritis,-Gouty-enzymology; Arthritis,-Gouty-genetics; Base-Sequence; Brain-enzymology; Cells,-Cultured; DNA-Binding-Proteins-metabolism; Enzyme-Induction; Hypoxanthine-Phosphoribosyltransferase-biosynthesis; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Mammals-genetics; Mammals-metabolism; Methylation-; Mice-; Mice,-Knockout; Mice,-Transgenic; Molecular-Sequence-Data; Nerve-Tissue-Proteins-biosynthesis; Nerve-Tissue-Proteins-deficiency; Nerve-Tissue-Proteins-genetics; Promoter-Regions-Genetics; Pseudogenes-; Purines-metabolism; Rodentia-genetics; Species-Specificity; Transcription-Factors-metabolism; X-Chromosome-genetics
MESH: *Gene-Expression-Regulation,-Enzymologic; *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Animal; Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: R01AR41996ARNIAMS
RN: EC 2.4.2.8; 0; 0; 0; 0; 125267-48-3
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Binding-Proteins; Nerve-Tissue-Proteins; Purines; Transcription-Factors; erythroid-specific-DNA-binding-factor
AN: 96236097
UD: 9609
MEDLINE EXPRESS (R) 1/96-12/96 7 of 122
TI: Methotrexate inhibits superoxide production and chemotaxis in neutrophils activated by granulocyte colony-stimulating factor.
AU: Okuda-A; Kubota-M; Sawada-M; Koishi-S; Kataoka-A; Bessho-R; Usami-I; Lin-YW; Adachi-S; Furusho-K
AD: Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
SO: J-Cell-Physiol. 1996 Jul; 168(1): 183-7
ISSN: 0021-9541
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Treatment of circulating human neutrophils with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for 30 min augmented superoxide generation and chemotaxis induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) in a dose dependent manner. When neutrophils were treated with 1 microM of methotrexate (MTX) for 60 min after incubation with rhG-CSF (10 ng/ml), the effects of rhG-CSF on superoxide generation and chemotaxis were inhibited by approximately 49 and 29%, respectively. Although inhibitory effects of MTX were also seen in neutrophils not pretreated with rhG-CSF, the degree of inhibition was much less. The addition of either hypoxanthine or guanosine at a concentration of 100 microM to the culture medium significantly attenuated the effects of MTX. However, in neutrophils obtained from a patient with Lesch-Nyhan syndrome, which lacked hypoxanthine-guanine phosphoribosyl transferase activity neither hypoxanthine nor guanosine had any rescue effect. These results suggest that MTX inhibits superoxide generation and chemotaxis in rhG-CSF-activated neutrophils, at least in part, by disturbing purine nucleotide biosynthesis.
MESH: Cells,-Cultured; Guanosine-pharmacology; Hypoxanthines-pharmacology; Lesch-Nyhan-Syndrome; Leucovorin-pharmacology; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Recombinant-Proteins
MESH: *Chemotaxis,-Leukocyte-drug-effects; *Folic-Acid-Antagonists-pharmacology; *Granulocyte-Colony-Stimulating-Factor-pharmacology; *Methotrexate-pharmacology; *Neutrophils-drug-effects; *Respiratory-Burst-drug-effects; *Superoxides-metabolism
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 11062-77-4; 118-00-3; 143011-72-7; 58-05-9; 59-05-2; 59880-97-6; 68-94-0
NM: Folic-Acid-Antagonists; Hypoxanthines; Recombinant-Proteins; Superoxides; Guanosine; Granulocyte-Colony-Stimulating-Factor; Leucovorin; Methotrexate; N-Formylmethionine-Leucyl-Phenylalanine; hypoxanthine
AN: 96257849
UD: 9609
MEDLINE EXPRESS (R) 1/96-12/96 8 of 122
TI: Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.
AU: Wong-DF; Harris-JC; Naidu-S; Yokoi-F; Marenco-S; Dannals-RF; Ravert-HT; Yaster-M; Evans-A; Rousset-O; Bryan-RN; Gjedde-A; Kuhar-MJ; Breese-GR
AD: Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
SO: Proc-Natl-Acad-Sci-U-S-A. 1996 May 28; 93(11): 5539-43
ISSN: 0027-8424
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders.
MESH: Adolescence-; Adult-; Brain-pathology; Brain-radionuclide-imaging; Carbon-Radioisotopes-diagnostic-use; Cerebellum-metabolism; Cerebellum-pathology; Cerebellum-radionuclide-imaging; Cocaine-analogs-and-derivatives; Cocaine-diagnostic-use; Cocaine-metabolism; Corpus-Striatum-metabolism; Corpus-Striatum-pathology; Corpus-Striatum-radionuclide-imaging; Dopamine-Uptake-Inhibitors-diagnostic-use; Dopamine-Uptake-Inhibitors-metabolism; Kinetics-; Lesch-Nyhan-Syndrome-radionuclide-imaging; Magnetic-Resonance-Imaging; Middle-Age; Nerve-Tissue-Proteins-metabolism; Organ-Specificity; Putamen-metabolism; Putamen-pathology; Putamen-radionuclide-imaging; Reference-Values; Rett-Syndrome-radionuclide-imaging; Time-Factors; Tomography,-Emission-Computed
MESH: *Brain-metabolism; *Carrier-Proteins-metabolism; *Lesch-Nyhan-Syndrome-metabolism; *Rett-Syndrome-metabolism
TG: Comparative-Study; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD23042HDNICHD; HD24061HDNICHD; NS15080NSNINDS
RN: 0; 0; 0; 0; 0; 50-36-2; 50370-56-4
NM: dopamine-binding-protein; Carbon-Radioisotopes; Carrier-Proteins; Dopamine-Uptake-Inhibitors; Nerve-Tissue-Proteins; Cocaine; Win-35428
AN: 96224321
UD: 9609
MEDLINE EXPRESS (R) 1/96-12/96 9 of 122
TI: New approaches to understanding Lesch-Nyhan disease [editorial; comment]
CM: Comment on: N Engl J Med 1996 Jun 13;334(24):1568-72
AU: Nyhan-WL; Wong-DF
SO: N-Engl-J-Med. 1996 Jun 13; 334(24): 1602-4
ISSN: 0028-4793
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
MESH: Brain-radionuclide-imaging; Brain-Chemistry-genetics; Brain-Chemistry-physiology; Gene-Therapy; Hypoxanthine-Phosphoribosyltransferase-deficiency; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-therapy
MESH: *Brain-Chemistry; *Hypoxanthine-Phosphoribosyltransferase; *Lesch-Nyhan-Syndrome-enzymology
TG: Human
PT: COMMENT; EDITORIAL
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 96221885
UD: 9608
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 10 of 122
TI: Presynaptic dopaminergic deficits in Lesch-Nyhan disease [see comments]
CM: Comment in: N Engl J Med 1996 Jun 13;334(24):1602-4
AU: Ernst-M; Zametkin-AJ; Matochik-JA; Pascualvaca-D; Jons-PH; Hardy-K; Hankerson-JG; Doudet-DJ; Cohen-RM
AD: Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA.
SO: N-Engl-J-Med. 1996 Jun 13; 334(24): 1568-72
ISSN: 0028-4793
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: BACKGROUND: Lesch-Nyhan disease is a rare, devastating, X-linked recessive disorder of purine synthesis. Patients present with hyperuricemia, choreoathetosis, dystonia, and aggressive and self-injurious behavior. Although the genetic and biochemical abnormalities have been identified, the causes of the neuropsychiatric syndrome remain unclear. METHODS: We used positron-emission tomography to measure presynaptic accumulation of fluorodopa F 18 tracer in the dopaminergic regions of the brains of 12 patients with Lesch-Nyhan disease (age, 10 to 20 years) and 15 healthy controls (age, 12 to 23). The results were expressed as ratios of specific to nonspecific radioactive counts. A low ratio indicates decreased dopa decarboxylase activity and dopamine storage. RESULTS: The fluorodopa F 18 ratio was significantly lower in the putamen (31 percent of control values), caudate nucleus (39 percent), frontal cortex (44 percent), and ventral tegmental complex (substantia nigra and ventral tegmentum; 57 percent) in the patients with Lesch-Nyhan disease than in the controls. Uptake of the tracer was abnormally low even in the youngest patients tested, and there was no overlap in the values between patients and controls. CONCLUSIONS: Patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggests that they contribute to the characteristic neuropsychiatric manifestations of the disease.
MESH: Adolescence-; Adult-; Analysis-of-Variance; Brain-pathology; Caudate-Nucleus-chemistry; Caudate-Nucleus-pathology; Caudate-Nucleus-radionuclide-imaging; Cerebral-Cortex-chemistry; Cerebral-Cortex-pathology; Cerebral-Cortex-radionuclide-imaging; Child-; Dopa-analogs-and-derivatives; Dopa-diagnostic-use; Fluorine-Radioisotopes-diagnostic-use; Lesch-Nyhan-Syndrome-radionuclide-imaging; Presynaptic-Terminals-chemistry; Presynaptic-Terminals-radionuclide-imaging; Putamen-chemistry; Putamen-pathology; Putamen-radionuclide-imaging; Receptors,-Dopamine-deficiency; Receptors,-Presynaptic-deficiency; Tomography,-Emission-Computed
MESH: *Brain-radionuclide-imaging; *Brain-Chemistry; *Lesch-Nyhan-Syndrome-pathology; *Presynaptic-Terminals; *Receptors,-Dopamine-analysis; *Receptors,-Presynaptic-analysis
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 63-84-3; 75290-51-6
NM: Fluorine-Radioisotopes; Receptors,-Dopamine; Receptors,-Presynaptic; Dopa; fluorodopa-F-18
AN: 96221877
UD: 9608
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 11 of 122
TI: Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells.
AU: Hakoda-M; Hirai-Y; Akiyama-M; Yamanaka-H; Terai-C; Kamatani-N; Kashiwazaki-S
AD: Institute of Rheumatology, Tokyo Women's Medical College, Japan.
SO: Hum-Genet. 1995 Dec; 96(6): 674-80
ISSN: 0340-6717
PY: 1995
LA: ENGLISH
CP: GERMANY
AB: Lesch-Nyhan syndrome is caused by a severe genetic deficiency of hypoxanthine phosphoribosyltransferase (HPRT) and is characterized by central nervous system disorders, gout, and in some cases, macrocytic anemia. Women heterozygous for HPRT deficiency are healthy but their somatic cells are mosaic for enzyme deficiency owing to random inactivation of the X chromosome. Frequencies of red blood cells and T cells deficient in HPRT are significantly lower than the expected 50% in heterozygotes, suggesting that HPRT-negative blood cells are selected against in heterozygotes. To determine at which stage of hematopoiesis such selection occurs, we determined the frequencies of HPRT-negative T, B and erythroid precursor cells in three heterozygotes. Since the cloning efficiencies of T and B cells and colony forming efficiency of burst-forming unit erythroid (BFU-E) for sample from Lesch-Nyhan patients were similar to those of normal cells, HPRT deficiency does not seem to render the differentiated cells less efficient for proliferation. However, the frequencies of HPRT-negative T and B cells, and BFU-E were all less than 10% in each of the three heterozygotes. Although the frequencies of HPRT-negative cells showed tenfold variations between the heterozygotes, each heterozygote had similar frequencies of HPRT-negative cells in the three cell types. These results suggest that HPRT is important at early stages of hematopoiesis, but less so after the cells have differentiated into T cells, B cells and erythroid precursor cells.
MESH: Adult-; B-Lymphocytes-enzymology; Cell-Line; Clone-Cells; Erythrocytes-enzymology; Hematopoiesis-; Heterozygote-Detection; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-blood; Organ-Specificity; T-Lymphocytes-enzymology; Thioguanine-pharmacology
MESH: *Hematopoietic-Stem-Cells-enzymology; *Heterozygote-; *Hypoxanthine-Phosphoribosyltransferase-blood; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-enzymology; *Lesch-Nyhan-Syndrome-genetics; *X-Chromosome
TG: Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 154-42-7
NM: Hypoxanthine-Phosphoribosyltransferase; Thioguanine
AN: 96101893
UD: 9603
MEDLINE EXPRESS (R) 1/96-12/96 12 of 122
TI: Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome.
AU: Renwick-PJ; Birley-AJ; McKeown-CM; Hulten-M
AD: Regional Genetic Laboratory Service, East Birmingham NHS Hospital Trust, UK.
SO: Clin-Genet. 1995 Aug; 48(2): 80-4
ISSN: 0009-9163
PY: 1995
LA: ENGLISH
CP: DENMARK
AB: Whole genomic hprt clones were used in Southern analysis to screen the integrity of the hprt gene in a family that includes a patient with HPRT enzyme deficiency causal to Lesch-Nyhan syndrome. A 5 kb DNA sequence deletion was found to have its endpoints in the first and third introns. The probes identified the carrier status of female family members, aided by an RFLP carried by the mother's normal X-chromosome.
MESH: Adult-; Blotting,-Southern; Chromosome-Mapping; Heterozygote-
MESH: *Gene-Deletion; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 96049827
UD: 9602
MEDLINE EXPRESS (R) 1991-1995 13 of 122
TI: Cognitive functioning in Lesch-Nyhan syndrome.
AU: Matthews-WS; Solan-A; Barabas-G
AD: Department of Pediatrics, University of Medicine and Dentistry of New Jersey, New Brunswick, USA.
SO: Dev-Med-Child-Neurol. 1995 Aug; 37(8): 715-22
ISSN: 0012-1622
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: The present study represents the first effort to assess systematically the cognitive functioning of a population of individuals with Lesch-Nyhan syndrome using standardized psychometric instruments. Seven residents from a special hospital setting participated. They ranged in age from 10 years 1 month to 22 years 3 months (mean 13 years 7 months). Using the Stanford-Binet Intelligence Scale: IV, scores in each of the four domains assessed by this battery (Verbal Reasoning, Abstract/Visual Reasoning, Quantitative and Short-Term Memory), as well as the general composite score, ranged from moderately mentally retarded to low average. Areas of weakness included attention, the manipulation of complex visual images, the comprehension of complex or lengthy speech, mathematical ability, and multi-step reasoning.
MESH: Adolescence-; Adult-; Anxiety-psychology; Child-; Cognition-Disorders-diagnosis; Cognition-Disorders-etiology; Intelligence-Tests; Lesch-Nyhan-Syndrome-complications; Memory,-Short-Term-physiology
MESH: *Cognition-; *Lesch-Nyhan-Syndrome-psychology
TG: Human; Male
PT: JOURNAL-ARTICLE
AN: 95402589
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 14 of 122
TI: Lesch-Nyhan syndrome: carrier and prenatal diagnosis.
AU: Alford-RL; Redman-JB; O'Brien-WE; Caskey-CT
AD: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
SO: Prenat-Diagn. 1995 Apr; 15(4): 329-38
ISSN: 0197-3851
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: We report the results of carrier and prenatal diagnosis for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, Lesch-Nyhan syndrome, by carrier testing of 83 women and prenatal analysis of 26 pregnancies. Our diagnostic methodologies include mutation detection and linkage analysis for probands and their families and biochemical measurement of HPRT enzyme activity for at-risk pregnancies. Identification of the mutation in the index case of each family permits precise carrier diagnosis using polymerase chain reaction (PCR) amplification of HPRT gene sequences and automated DNA sequencing. We demonstrate 100 per cent sensitivity for the detection of mutations in the HPRT gene of affected males and highly efficient carrier testing of at-risk females. Two other molecular methods proven to have high utility include PCR-based dosage analysis and linkage analysis by PCR amplification of a short tandem repeat (STR) in intron 3 of the HPRT gene. As a result, 45 at-risk women, 56 per cent of those tested, were identified not to be carriers of their family's HPRT gene mutation. Seven of these women were the mothers of affected males and prenatal testing for future pregnancies was recommended because of the possibility of gonadal mosaicism. Thirty-eight of these women were more distant relatives of affected males, thereby eliminating the need for future prenatal procedures. These studies illustrate the utility and precision of molecular methodologies for carrier and prenatal diagnosis of Lesch-Nyhan syndrome. These studies also illustrate that molecular diagnostic studies of affected males and carrier testing prior to pregnancy can clarify genetic risk predictions and eliminate unnecessary prenatal procedures.
MESH: Chromosome-Mapping; Hypoxanthine-Phosphoribosyltransferase-metabolism; Pedigree-; Polymerase-Chain-Reaction; Pregnancy-; Pregnancy,-High-Risk; Sensitivity-and-Specificity; Sequence-Analysis,-DNA
MESH: *Heterozygote-Detection-methods; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-diagnosis; *Prenatal-Diagnosis-methods
TG: Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO1DK31428DKNIDDK
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 95342801
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 15 of 122
TI: Gene therapy and the brain.
AU: Jinnah-HA; Friedmann-T
AD: Department of Neurology, Johns Hopkins University Hospital, Baltimore, MD, USA.
SO: Br-Med-Bull. 1995 Jan; 51(1): 138-48
ISSN: 0007-1420
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: In this article we describe the application of the emerging concepts of gene therapy to 4 different neurologic disorders. The first of these is Lesch-Nyhan disease, a genetically-determined neurodevelopmental disorder caused by a defect in the gene which encodes the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Two additional disorders, Parkinsonism and Alzheimer's disease, are both neurodegenerative diseases of unknown etiology which affect the elderly. The final disorder involves malignant brain tumors. In each of these disorders, basic research with in vitro systems and animal models has suggested that the tools of gene transfer may provide a novel and potentially effective treatment strategy.
MESH: Gene-Transfer; Genetic-Vectors; Infant,-Newborn; Rats-
MESH: *Alzheimer's-Disease-therapy; *Brain-Neoplasms-therapy; *Gene-Therapy-methods; *Lesch-Nyhan-Syndrome-therapy; *Parkinson-Disease-therapy
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-ACADEMIC
RN: 0
NM: Genetic-Vectors
AN: 95285150
UD: 9509
MEDLINE EXPRESS (R) 1991-1995 16 of 122
TI: Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.
AU: Jinnah-HA; Wojcik-BE; Hunt-M; Narang-N; Lee-KY; Goldstein-M; Wamsley-JK; Langlais-PJ; Friedmann-T
AD: Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093.
SO: J-Neurosci. 1994 Mar; 14(3 Pt 1): 1164-75
ISSN: 0270-6474
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.
MESH: Aging-metabolism; Caudate-Nucleus-metabolism; Disease-Models,-Animal; Dopamine-genetics; Hydroxyindoleacetic-Acid-metabolism; Hypoxanthine-Phosphoribosyltransferase-genetics; Hypoxanthine-Phosphoribosyltransferase-metabolism; Lesch-Nyhan-Syndrome-genetics; Mice-; Mutation-; Norepinephrine-metabolism; Phencyclidine-analogs-and-derivatives; Phencyclidine-metabolism; Putamen-metabolism; Serotonin-metabolism; Tryptophan-Hydroxylase-metabolism; 3,4-Dihydroxyphenylacetic-Acid-metabolism
MESH: *Brain-metabolism; *Dopamine-deficiency; *Lesch-Nyhan-Syndrome-metabolism
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD20034HDNICHD; RR04754RRNCRR
RN: EC 1.14.16.4; EC 2.4.2.8; 102-32-9; 112726-66-6; 50-67-9; 51-41-2; 51-61-6; 54-16-0; 77-10-1
NM: Tryptophan-Hydroxylase; Hypoxanthine-Phosphoribosyltransferase; 3,4-Dihydroxyphenylacetic-Acid; GK-13; Serotonin; Norepinephrine; Dopamine; Hydroxyindoleacetic-Acid; Phencyclidine
AN: 94165772
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 17 of 122
TI: Direct evidence for a hot spot of germline mutation at HPRT locus.
AU: Fujimori-S; Tagaya-T; Yamaoka-N; Saito-H; Kamatani-N; Akaoka-I
AD: Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
SO: Adv-Exp-Med-Biol. 1994; 370: 679-82
ISSN: 0065-2598
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Amino-Acid-Sequence; Base-Sequence; Exons-; Family-; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Polymerase-Chain-Reaction
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Point-Mutation
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 95390075
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 18 of 122
TI: Plasma and urinary oxypurines in Lesch-Nyhan patient after allopurinol treatment.
AU: Roscioni-G; Farnetani-MA; Pagani-R; Pizzichini-M; Marinello-E; Porcelli-B
AD: Institute of Pediatrics, University of Siena, Italy.
SO: Adv-Exp-Med-Biol. 1994; 370: 357-61
ISSN: 0065-2598
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Child-; Erythrocytes-enzymology; Fibroblasts-enzymology; Hypoxanthine-Phosphoribosyltransferase-blood; Hypoxanthines-blood; Hypoxanthines-urine; Lesch-Nyhan-Syndrome-urine; Purines-urine; Uric-Acid-blood; Uric-Acid-urine; Xanthines-blood; Xanthines-urine
MESH: *Hypoxanthine-Phosphoribosyltransferase-metabolism; *Lesch-Nyhan-Syndrome-blood; *Lesch-Nyhan-Syndrome-drug-therapy; *Purines-blood
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0; 0; 68-94-0; 69-89-6; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Hypoxanthines; Purines; Xanthines; hypoxanthine; xanthine; Uric-Acid
AN: 95390004
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 19 of 122
TI: Treatment of Lesch-Nyhan syndrome with AICAR.
AU: Page-T; Barshop-B; Yu-AL; Nyhan-WL
AD: Department of Pediatrics, University of California, San Diego, La Jolla 92093, USA.
SO: Adv-Exp-Med-Biol. 1994; 370: 353-6
ISSN: 0065-2598
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Adolescence-; Aminoimidazole-Carboxamide-administration-and-dosage; Aminoimidazole-Carboxamide-pharmacokinetics; Aminoimidazole-Carboxamide-therapeutic-use; Hypoxanthines-blood; Hypoxanthines-urine; Infusions,-Intravenous; Lesch-Nyhan-Syndrome-complications; Lesch-Nyhan-Syndrome-metabolism; Leukemia-complications; Leukemia-metabolism; Oxypurinol-urine; Ribonucleotides-administration-and-dosage; Ribonucleotides-pharmacokinetics; Uric-Acid-blood; Uric-Acid-urine; Xanthines-blood; Xanthines-urine
MESH: *Aminoimidazole-Carboxamide-analogs-and-derivatives; *Lesch-Nyhan-Syndrome-drug-therapy; *Ribonucleotides-therapeutic-use
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 2465-59-0; 3031-94-5; 360-97-4; 68-94-0; 69-89-6; 69-93-2
NM: Hypoxanthines; Ribonucleotides; Xanthines; Oxypurinol; AICA-ribonucleotide; Aminoimidazole-Carboxamide; hypoxanthine; xanthine; Uric-Acid
AN: 95390003
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 20 of 122
TI: Molecular mechanisms of the second female Lesch-Nyhan patient.
AU: Yamada-Y; Goto-H; Yukawa-T; Akazawa-H; Ogasawara-N
AD: Department of Genetics, Institute for Developmental Research, Aichi Prefectural Colony, Japan.
SO: Adv-Exp-Med-Biol. 1994; 370: 337-40
ISSN: 0065-2598
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Adenine-Phosphoribosyltransferase-blood; Amino-Acid-Sequence; Base-Sequence; Child-; Deoxyribonucleases,-Type-II-Site-Specific; Erythrocytes-enzymology; Exons-; Genes,-Recessive; Hypoxanthine-Phosphoribosyltransferase-blood; Karyotyping-; Molecular-Sequence-Data; Reference-Values; Restriction-Mapping; RNA,-Messenger-analysis; Sex-Characteristics
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-enzymology; *Lesch-Nyhan-Syndrome-genetics
TG: Case-Report; Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.7; EC 2.4.2.8; EC 3.1.21.-; EC 3.1.21.4; 0
NM: Adenine-Phosphoribosyltransferase; Hypoxanthine-Phosphoribosyltransferase; endodeoxyribonuclease-XhoI; Deoxyribonucleases,-Type-II-Site-Specific; RNA,-Messenger
AN: 95389998
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 21 of 122
TI: Genetic and clinical heterogeneity in hypoxanthine phosphoribosyltransferase deficiencies.
AU: Burgemeister-R; Gutensohn-W; Van-den-Berghe-G; Jaeken-J
AD: Institute of Anthropology and Human Genetics, University of Munich, Germany.
SO: Adv-Exp-Med-Biol. 1994; 370: 331-5
ISSN: 0065-2598
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Base-Sequence; DNA-Primers; Erythrocytes-enzymology; Exons-; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Polymorphism-Genetics; Purine-Pyrimidine-Metabolism,-Inborn-Errors-enzymology
MESH: *Frameshift-Mutation; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Point-Mutation; *Purine-Pyrimidine-Metabolism,-Inborn-Errors-genetics
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Primers
AN: 95389997
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 22 of 122
TI: Theory and practice of psychopharmacogenetics.
AU: Tu-JB
AD: Department of Psychiatry, University of Western Ontario, London, Canada.
SO: Am-J-Med-Genet. 1994 Dec 15; 54(4): 391-7
ISSN: 0148-7299
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: This article attempts to elucidate the theory and practice of psychopharmacogenetics. Eight working models were identified and characterized with a distinct view of risk factors in the host, the pathophysiology of disease, and the strategies for optimum therapy. The biochemical culprits related to adverse drug reaction in each case can be used to identify a risk and thus contribute to prevention research. Since the phenomenology of these uncommon conditions covers a broad spectrum of neuropsychiatric manifestations, the insights they generated might presage a better understanding of the natural history of a wider range of mental disorders associated with genetic vulnerability. The emerging information suggests that psychopharmacogenetics could be defined from clinical perspectives as multidimensional analysis of genes, drugs, and behaviour for the treatment and prevention of psychiatric disorders.
MESH: Child-; Down-Syndrome-genetics; Hemochromatosis-genetics; Hepatolenticular-Degeneration-diagnosis; Hepatolenticular-Degeneration-genetics; Huntington's-Disease-genetics; Lesch-Nyhan-Syndrome-genetics; Phenylketonuria-diagnosis; Phenylketonuria-prevention-and-control; Porphyria-chemically-induced; Prader-Willi-Syndrome-genetics
MESH: *Genetics,-Behavioral; *Hereditary-Diseases-genetics; *Models,-Genetic; *Psychopharmacology-; *Psychotropic-Drugs-adverse-effects
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0
NM: Psychotropic-Drugs
AN: 95243276
UD: 9507
MEDLINE EXPRESS (R) 1991-1995 23 of 122
TI: Ultrastructure of Met5-enkephalin terminals in the caudate-putamen nuclei of adult rats receiving neonatal intranigral 6-hydroxydopamine.
AU: Pickel-VM; Chan-J; Pierce-JP
AD: Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
SO: Brain-Res-Dev-Brain-Res. 1994 Dec 16; 83(2): 163-80
ISSN: 0165-3806
PY: 1994
LA: ENGLISH
CP: NETHERLANDS
AB: Destruction of dopamine neurons of the nigrostriatal pathway in the early postnatal rat enhances the levels of Met5-enkephalin in the adult dorsal striatum (caudate-putamen nuclei) and may contribute to the abnormal self-injurious behavior seen in humans with Lesch-Nyhan disease. We examined whether there were ultrastructural changes in Met5-enkephalin immunoreactive terminals in the rat model that might reflect cellular sites for enhanced activity of these opioid neurons. At 3 days postnatal, 10-20 nl injections of a 1% solution of the dopamine neurotoxin, 6-hydroxydopamine (6-OHDA), or vehicle were placed unilaterally in the region of the substantia nigra of 25 litters of male rat pups. In adulthood (72-80 days postnatal), the brains of these animals were fixed by vascular perfusion with an aldehyde solution. Met5-enkephalin immunolabeling was examined in coronal sections at three rostrocaudal levels through the caudate-putamen nuclei of control (ipsilateral and contralateral to vehicle and contralateral to 6-OHDA) and experimental (ipsilateral to 6-OHDA) groups. In selectively lesioned animals, there was a significant increase in the relative optical density of immunoautoradiographic labeling for enkephalin throughout the rostrocaudal striatum ipsilateral to 6-OHDA as compared to control groups. Electron microscopy revealed immunoperoxidase labeling for enkephalin in axon terminals and more rarely in soma and dendrites irrespective of drug treatment. In both experimental and control striatal tissues, the enkephalin immunoreactive terminals formed primarily symmetric synapses with unlabeled dendrites or spines. However, ipsilateral to 6-OHDA injections there was a small (5.4%), but significant increase in the proportion of enkephalin immunoreactive terminals contacting dendritic spines, the known targets of dopamine terminals. Appositions were commonly detected between enkephalin immunoreactive terminals and other morphologically heterogeneous axons in the striatum ipsilateral to 6-OHDA and in control tissues. Met5-enkephalin immunoreactive terminals in adult striatum ipsilateral to 6-OHDA injections showed a 214% increase in volume as compared to vehicle-injected controls. Concurrently, there was a small (13%), but significant increase in the numerical density (number/volume) of enkephalin-labeled terminals both contralateral and ipsilateral to 6-OHDA injections. These results suggest that a change in bouton size is the major mechanism by which striatal enkephalin neurons alter their synaptic efficacy and target associations to compensate for damage to the nigrostriatal dopamine neurons.
MESH: Autoradiography-; Dopamine-metabolism; Enkephalin,-Methionine-metabolism; Enkephalins-metabolism; Immunohistochemistry-; Lesch-Nyhan-Syndrome-metabolism; Microscopy,-Electron; Neostriatum-chemistry; Neostriatum-ultrastructure; Protein-Precursors-metabolism; Rats-; Synapses-drug-effects; Synapses-ultrastructure
MESH: *Enkephalin,-Methionine-analysis; *Enkephalins-analysis; *Neostriatum-drug-effects; *Oxidopamine-; *Protein-Precursors-analysis; *Receptors,-Opioid-drug-effects; *Synapses-
TG: Animal; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: MH40342MHNIMH; DA04600DANIDA; MH00078MHNIMH
RN: 0; 0; 0; 1199-18-4; 51-61-6; 58569-55-4; 93443-35-7
NM: Enkephalins; Protein-Precursors; Receptors,-Opioid; Oxidopamine; Dopamine; Enkephalin,-Methionine; preproenkephalin
AN: 95212007
UD: 9507
MEDLINE EXPRESS (R) 1991-1995 24 of 122
TI: Serial renal sonographic evaluation of patients with Lesch-Nyhan syndrome.
AU: Rosenfeld-DL; Preston-MP; Salvaggi-Fadden-K
AD: Department of Radiology, Robert Wood Johnson University Hospital, New Brunswick, NJ 08903.
SO: Pediatr-Radiol. 1994; 24(7): 509-12
ISSN: 0301-0449
PY: 1994
LA: ENGLISH
CP: GERMANY
AB: The objective of this study was to review sequential renal sonograms of patients with Lesch-Nyhan syndrome obtained over several years to determine different sonographic patterns, the alterations in the patterns occurring over time and the relationship to management. Additional objectives were to evaluate the size of the kidneys, and to correlate the metabolic constituents of calculi with the therapeutic regimens and with the renal sonographic patterns. Serial sonograms of six patients with Lesch-Nyhan syndrome were reviewed for periods varying between 2 and 7 years with a mean of 4 years. The ages of the patients at the conclusion of the study were between 10 and 22 years. Three patterns of abnormal echogenicity were found; a punctate increase in echogenicity in the renal medullary pyramids, a diffuse increase in medullary pyramid echogenicity, and a pattern of increased echogenicity in the collecting system. These patterns were progressive but did not alternate on sequential scans, regardless of increasing or constant therapy. Analysis of calculi suggested patients were precipitating various metabolites concurrently; the incidence of metabolites appeared to be unrelated to therapy. Those patients with shadowing opacities, whether in the renal medulla or collecting system, were more likely to develop renal colic. Renal dimensions were small with renal function remaining normal.
MESH: Adolescence-; Child-; Child,-Preschool; Kidney-Calculi-chemistry; Kidney-Calculi-etiology; Uric-Acid-analysis; Xanthines-analysis
MESH: *Kidney-ultrasonography; *Kidney-Calculi-ultrasonography; *Lesch-Nyhan-Syndrome-complications
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 69-93-2
NM: Xanthines; Uric-Acid
AN: 95192000
UD: 9506
MEDLINE EXPRESS (R) 1991-1995 25 of 122
TI: Lesch-Nyhan Syndrome: report on two brothers.
AU: Yang-MT; Mak-SC; Chi-CS; Lin-HY; Lii-YP; Wu-KH; Shian-WJ
AD: Department of Pediatrics, Taichung Veterans General Hospital, R.O.C.
SO: Acta-Paediatr-Sin. 1994 Nov-Dec; 35(6): 552-8
ISSN: 0001-6578
PY: 1994
LA: ENGLISH
CP: TAIWAN
AB: Lesch-Nyhan syndrome is a rare X-linked disease characterized by over-production of uric acid and a central nervous system (CNS) disorder consisting of mental retardation, spasticity, choreoathetosis, and a compulsive form of self-mutilation. A deficiency in hypoxanthine-guanine phosphoribosyl transferase (HPRT) provides the underlying metabolic basis for this disease. A 12 month-old male baby who had orange crystals over the diapers since he was 3 months old was brought to our hospital due to developmental delay. Mental retardation and athetosis were also noted. Chemical analysis revealed hyperuricemia (uric acid 8.6 mg/dl). Urine routine showed microscopic hematuria and uric acid crystals. The activity of HPRT in erythrocyte lysates of parents were both within normal limits, but that of the patient was very low (0.0547 nm/min/mg protein, < 0.05% of control). His younger brother was born 2 months after this disorder diagnosed in this patient. The younger brother was noted to have uric acid crystals over the diapers when he was 40 days old and hyperuricemia (10.6 mg/dl) showed up later. He was also a case of Lesch-Nyhan syndrome since the activity of HPRT in erythrocyte lysates was also low (0.0327 nmol/min/mg protein, < 0.05% of control). Further studies, including carrier detection and deoxyribonucleic acid (DNA) analysis, could be helpful for genetic counseling. This syndrome is rare among Chinese, and this may be due to underdiagnosis.
MESH: Family-Health; Hypoxanthine-Phosphoribosyltransferase-deficiency; Infant-; Lesch-Nyhan-Syndrome-genetics; Uric-Acid-blood; Uric-Acid-urine
MESH: *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Uric-Acid
AN: 95133380
UD: 9504
MEDLINE EXPRESS (R) 1991-1995 26 of 122
TI: Lesch-Nyhan syndrome. A case report.
AU: Smith-BM; Cutilli-BJ; Fedele-M
AD: Department of Oral and Maxillofacial Surgery, Temple University School of Dentistry, Philadelphia, Pa.
SO: Oral-Surg-Oral-Med-Oral-Pathol. 1994 Sep; 78(3): 317-8
ISSN: 0030-4220
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Lesch-Nyhan syndrome is a rare anomaly consisting of a deficiency in the production of hypoxanthine phosphoribosyltransferase that leads to the overproduction of purine and the accumulation of uric acid. Major manifestations include mental retardation and self-destructive behavior resulting in self-mutilation through biting and scratching. Because no medical treatment exists to alleviate the symptoms of self-mutilation, direct dental intervention is the only way these behaviors can be affected. A unique case of this type involving two male identical twins is reported.
MESH: Child-; Lip-injuries; Tongue-injuries
MESH: *Diseases-in-Twins; *Lesch-Nyhan-Syndrome-physiopathology; *Self-Mutilation-surgery; *Tooth-Extraction
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 95060683
UD: 9502
SB: DENTAL
MEDLINE EXPRESS (R) 1991-1995 27 of 122
TI: Murine genetic models of human disease.
AU: Clarke-AR
AD: Department of Pathology, University Medical School, Edinburgh, UK.
SO: Curr-Opin-Genet-Dev. 1994 Jun; 4(3): 453-60
ISSN: 0959-437X
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: Until recently, good animal models of human disease have been available only in limited numbers, largely because of technical difficulties associated with transgenesis. As a consequence of recent rapid advances principally, but not exclusively, focused around the use of embryonic stem cells, it is now theoretically possible to model the genetic lesion underlying any human disease in the mouse. This has led not only to a better understanding of complex disease processes, such as those associated with malignancy, but, as in the cases of cystic fibrosis and duchenne muscular dystrophy, is now allowing the development of novel therapy regimes.
MESH: Lesch-Nyhan-Syndrome-genetics; Mice-; Mice,-Mutant-Strains; Muscular-Dystrophy,-Animal-genetics; Neoplasms,-Experimental-genetics
MESH: *Disease-Models,-Animal; *Models,-Genetic
TG: Animal; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 95003635
UD: 9501
MEDLINE EXPRESS (R) 1991-1995 28 of 122
TI: Purine metabolism in Lesch-Nyhan syndrome versus Kelley-Seegmiller syndrome.
AU: Mateos-EA; Puig-JG
AD: Division of Clinical Biochemistry, La Paz Hospital, Universidad Autonoma, Madrid, Spain.
SO: J-Inherit-Metab-Dis. 1994; 17(1): 138-42
ISSN: 0141-8955
PY: 1994
LA: ENGLISH
CP: NETHERLANDS
MESH: Adolescence-; Adult-; Aged-; Child-; Child,-Preschool; Erythrocytes-enzymology; Gout-enzymology; Gout-metabolism; Hypoxanthine-Phosphoribosyltransferase-blood; Middle-Age; Phenotype-; Purine-Pyrimidine-Metabolism,-Inborn-Errors-enzymology; Syndrome-
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-metabolism; *Purine-Pyrimidine-Metabolism,-Inborn-Errors-metabolism
TG: Comparative-Study; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 94328591
UD: 9411
MEDLINE EXPRESS (R) 1991-1995 29 of 122
TI: [Lesch-Nyhan syndrome (editorial; comment)]
TO: Sindrome de Lesch-Nyhan.
CM: Comment on: Med Clin (Barc) 1994 May 14;102(18):681-7
AU: Hernandez-Nieto-L
SO: Med-Clin-Barc. 1994 May 14; 102(18): 699-700
ISSN: 0025-7753
PY: 1994
LA: SPANISH; NON-ENGLISH
CP: SPAIN
MESH: Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-genetics
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome
TG: Human
PT: COMMENT; EDITORIAL
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 94301062
UD: 9410
MEDLINE EXPRESS (R) 1991-1995 30 of 122
TI: [Clinical spectrum of hypoxanthine-guanine phosphoribosyltransferase deficiency: study of 12 cases (see comments)]
TO: Espectro clinico de la deficiencia de hipoxantina-guanina fosforribosiltransferasa: estudio de 12 pacientes.
CM: Comment in: Med Clin (Barc) 1994 may 14;102(18):699-700
AU: Garcia-Puig-J; Mateos-FA; Jimenez-ML; Arcas-J; Miranda-ME; Oriz-Vazquez-J
AD: Servicio de Medicina Interna, Hospital La Paz, Universidad Autonoma, Madrid.
SO: Med-Clin-Barc. 1994 May 14; 102(18): 681-7
ISSN: 0025-7753
PY: 1994
LA: SPANISH; NON-ENGLISH
CP: SPAIN
AB: BACKGROUND: The hypoxanthine-guanine phosphoribosyltransferase deficiency (HGPRT) may have two clinical forms: that of the Lesch-Nyhan syndrome (complete HGPRT deficiency) and that of the Kelley-Seegmiller syndrome (partial HGPRT deficiency). The clinical and biochemical features of the HGPRT deficiency are not completely known. METHODS: A series of 12 patients, 8 with the Lesch-Nyhan syndrome and 4 with the Kelley-Seegmiller syndrome are described. The plasma and urine concentrations of hypoxanthine, xanthine and uric acid were compared with those obtained in 20 normal subjects and 41 patients with primary gout. The molecular defect which determines the deficient HGPRT activity was studied in one patient with the Kelley-Seegmiller syndrome. RESULTS: The 8 patients with the Lesch-Nyhan syndrome presented choreoathetosis, corticospinal motor system dysfunction, mental retardation and signs of self mutilation. The neurologic manifestations of the patients with the Kelley-Seegmiller syndrome were very heterogeneous: two patients had psychomotor retardation with spastic movement, one was mentally retarded with generalized dystonia and one patient only had gout with no neurologic manifestations. The erythrocytic HGPRT activity ranged between 0.28 and < 0.01 nmol/h and mg of hemoglobin in all the patients. Plasma and urine purine concentrations were very high, being greater than those in normal subjects and patients with gout (p < 0.01). A mutation was identified in exon 3 (substitution of guanine with thymine) conditioning the substitution of the normal glycine amino acid by valine (HGPRT Madrid) on molecular study. CONCLUSIONS: The hypoxanthine-guanine phosphoribosyltransferase deficiency has a heterogeneous clinical expression. The activity of this enzyme in erythrocytes and the results of the metabolism of the purines do not allow prediction of the severity of the clinical manifestations.
MESH: Adult-; Base-Sequence; Child-; Child,-Preschool; English-Abstract; Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-metabolism; Molecular-Sequence-Data; Pedigree-; Point-Mutation; Purines-metabolism; Spain-
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; Purines
AN: 94301059
UD: 9410
MEDLINE EXPRESS (R) 1991-1995 31 of 122
TI: A self-controllable mask with helmet to prevent self finger-mutilation in the Lesch-Nyhan syndrome.
AU: Eguchi-S; Tokioka-T; Motoyoshi-A; Wakamura-S
AD: Kochi Prefectural Institute for Handicapped Children, Japan.
SO: Arch-Phys-Med-Rehabil. 1994 Jun; 75(6): 709-10
ISSN: 0003-9993
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Self-mutilation is a characteristic symptom of Lesch-Nyhan syndrome. We report a newly developed orthosis for managing self-mutilation of the fingers through biting. The orthosis has a plastic mask attached to a helmet; the patient can manage the mask with one hand to stop biting fingers on the other hand. This is a report of a 6-year-old boy who was able to control finger biting by using the orthosis. Eighteen months later he has stopped biting his fingers and no longer wears the orthosis.
MESH: Child-; Fingers-
MESH: *Lesch-Nyhan-Syndrome-complications; *Orthotic-Devices; *Self-Mutilation-prevention-and-control
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 94270973
UD: 9409
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 32 of 122
TI: Lesch-Nyhan syndrome in two brothers: why early diagnosis is essential [letter]
AU: Mangano-M; Azzia-N; Russo-A; Romeo-MA
SO: Clin-Pediatr-Phila. 1994 Feb; 33(2): 125-6
ISSN: 0009-9228
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
MESH: Follow-Up-Studies; Infant-; Lesch-Nyhan-Syndrome-genetics; Time-Factors
MESH: *Family-Health; *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: LETTER
AN: 94258851
UD: 9409
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 33 of 122
TI: Self-injury in Lesch-Nyhan disease.
AU: Anderson-LT; Ernst-M
AD: Department of Psychiatry, New York University Medical Center.
SO: J-Autism-Dev-Disord. 1994 Feb; 24(1): 67-81
ISSN: 0162-3257
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Parents of 40 patients with Lesch-Nyhan disease completed a questionnaire detailing developmental history, life course, management, medication, factors influencing variability and topography of self-injury. Several conclusions were reached. Characteristics: Biting was the predominant form, perhaps only because of the difficulty of preventing it. There was considerable variability in self-injury which was strongly related to stress rather than to operant influences. Even though patients could not inhibit self-injury they could predict it and request restraints. Aggression against others was as prevalent as self-injury. Management: Stress reduction, teeth extraction, and physical restraint were the most commonly used management techniques. Behavior modification was of limited efficacy. Benzodiazepines were the most commonly used medications for controlling self-injury. Outcome: The severity of self-injury did not change over years. Age of onset was a predictor of outcome. The earlier the age of onset the worse the self-injury eventually became. The discussion describes research strategies, suggests dimensions along which self-injury can be classified, and highlights behavior not commonly described in patients with Lesch-Nyhan disease.
MESH: Adolescence-; Adult-; Aggression-psychology; Arousal-; Child-; Child,-Preschool; Lesch-Nyhan-Syndrome-diagnosis; Parenting-psychology; Periodicity-; Self-Injurious-Behavior-classification; Self-Injurious-Behavior-prevention-and-control; Social-Environment
MESH: *Lesch-Nyhan-Syndrome-psychology; *Self-Injurious-Behavior-psychology
TG: Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 1T32MH18915MHNIMH
AN: 94245595
UD: 9408
MEDLINE EXPRESS (R) 1991-1995 34 of 122
TI: Lesch-Nyhan syndrome: successful prevention of lower lip ulceration caused by self-mutilation by use of mouth guard.
AU: Sugahara-T; Mishima-K; Mori-Y
AD: Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Osaka University, Japan.
SO: Int-J-Oral-Maxillofac-Surg. 1994 Feb; 23(1): 37-8
ISSN: 0901-5027
PY: 1994
LA: ENGLISH
CP: DENMARK
AB: Lesch-Nyhan syndrome (LNS) is a disorder caused by congenital absence of a purine metabolic enzyme, hypoxanthine guanine phosphoribosyl-transferase (HGPRT). This syndrome is characterized clinically by hyperuricemia and neurologic features including choreoathetoid spasticity, self-mutilation, and mental retardation. We report on a patient in whom self-mutilation of the lower lip was suppressed with the help of a mouth guard made from soft resin.
MESH: Infant-
MESH: *Lesch-Nyhan-Syndrome-therapy; *Lip-injuries; *Mouth-Protectors; *Self-Mutilation-prevention-and-control
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 94216734
UD: 9407
SB: DENTAL
MEDLINE EXPRESS (R) 1991-1995 35 of 122
TI: Molecular description of a hypoxanthine phosphoribosyltransferase gene deletion in Lesch-Nyhan syndrome.
AU: Fuscoe-JC; Nelsen-AJ
AD: Environmental Health Research and Testing Inc., Research Triangle Park, NC 27709.
SO: Hum-Mol-Genet. 1994 Jan; 3(1): 199-200
ISSN: 0964-6906
PY: 1994
LA: ENGLISH
CP: ENGLAND
MESH: Base-Sequence; Blotting,-Southern; Cell-Line; DNA-genetics; DNA-Primers; Exons-; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Repetitive-Sequences,-Nucleic-Acid
MESH: *Gene-Deletion; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Human; Male; Support,-U.S.-Gov't,-P.H.S.
GS: hprt
PT: JOURNAL-ARTICLE
CN: N43ES21001ESNIEHS
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Primers; DNA
AN: 94214445
UD: 9407
SI: GENBANK/S69936
MEDLINE EXPRESS (R) 1991-1995 36 of 122
TI: Lesch-Nyhan syndrome presenting with renal insufficiency in infancy and transient neonatal hypothyroidism.
AU: Jenkins-EA; Hallett-RJ; Hull-RG
AD: Department of Rheumatology, Portsmouth Hospitals.
SO: Br-J-Rheumatol. 1994 Apr; 33(4): 392-6
ISSN: 0263-7103
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: A 20-day-old male infant presented with acute renal failure. Three weeks later he developed acutely swollen, hot, red joints and tophi in his hands and feet. The serum uric acid was 2.2 mmol/l (normal 0.13-0.23 mmol/l) and the urinary oxypurine/creatinine ratio was 2.26 mmol (normal < 1.5 mmol). Complete deficiency of hypoxanthine guanine phosphoribosyl transferase (HGPRT) in intact erythrocytes confirmed Lesch-Nyhan syndrome. Neurological development was delayed and self-mutilation was observed at 22 months. Acute renal failure secondary to crystal nephropathy and tophaceous gout are unusual presenting features of this rare condition. This child also had transient neonatal hypothyroidism, which is not a recognized manifestation of the syndrome.
MESH: Erythrocytes-enzymology; Gout-etiology; Gout-metabolism; Gout-radiography; Hypothyroidism-physiopathology; Hypoxanthine-Phosphoribosyltransferase-blood; Infant,-Newborn; Lesch-Nyhan-Syndrome-blood; Time-Factors; Uric-Acid-blood; Uric-Acid-metabolism
MESH: *Hypothyroidism-etiology; *Kidney-Failure,-Acute-etiology; *Lesch-Nyhan-Syndrome-complications
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Uric-Acid
AN: 94207710
UD: 9407
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 37 of 122
TI: A 13 base pair deletion in exon 1 of HPRTIllinois forms a functional GUG initiation codon.
AU: Davidson-BL; Golovoy-N; Roessler-BJ
AD: Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0680.
SO: Hum-Genet. 1994 Mar; 93(3): 300-4
ISSN: 0340-6717
PY: 1994
LA: ENGLISH
CP: GERMANY
AB: More than 50 mutations in the human hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus have been described, yet only 2 alter the AUG initiation codon. One, variant HPRT1151, results in Lesch-Nyhan syndrome (LNS), and the other, HPRTIllinois, results in partial HPRT deficiency. Although previously undetectable, we used a sensitive gel assay to demonstrate that HPRTIllinois is not only active, but has a native Mr indistinguishable from normal. Confirmatory evidence of activity and native Mr is demonstrated following transfection of HPRT cells with expression plasmids containing cDNA sequences representing HPRTIllinois. These data provide support for the hypothesis that patient RT, or variant HPRTIllinois, is spared manifestations of the LNS as a result of translation at the newly formed GUG initiation codon.
MESH: Base-Composition; Base-Sequence; Cell-Line,-Transformed; DNA-; Exons-; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Syndrome-; Transfection-; Translation,-Genetic
MESH: *Codon-; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Sequence-Deletion
TG: Case-Report; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO1DK19045DKNIDDK
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; Codon; DNA
AN: 94171232
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 38 of 122
TI: Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: identification of point mutations in Japanese patients with Lesch-Nyhan syndrome and hereditary gout and their permanent expression in an HPRT-deficient mouse cell line.
AU: Tohyama-J; Nanba-E; Ohno-K
AD: Division of Child Neurology, Faculty of Medicine, Tottori University, Yonago, Japan.
SO: Hum-Genet. 1994 Feb; 93(2): 175-81
ISSN: 0340-6717
PY: 1994
LA: ENGLISH
CP: GERMANY
AB: Two different single nucleotide transitions of hypoxanthine-guanine phosphoribosyltransferase (HPRT) were identified in a Japanese patient with Lesch-Nyhan syndrome (LNS) and a patient with hereditary gout. HPRT enzyme activities in the two patients were severely deficient, but the size and amount of mRNA were normal according to Northern analysis. Entire coding regions of HPRT cDNAs were amplified by PCR and sequenced. A G-to-A substitution at base 208 in exon 3, which predicted glycine 70 to arginine, was detected in the LNS patient (identical mutation with HPRT Utrecht). A C-to-A substitution at base 73 in exon 2, which predicted proline 25 to threonine, was detected in the gout patient (designated HPRT Yonago). We transfected normal HPRT cDNA, mutant cDNA with HRPT Utrecht or mutant cDNA with HPRT Yonago, respectively, to HPRT-deficient mouse cells and isolated permanent expression cell lines. The HPRT-deficient mouse cells had no detectable HPRT activity and a very low amount of HPRT mRNA. When the HPRT-deficient mouse cells were transfected with normal human cDNA, HPRT enzyme activity increased to 21.8% that of normal mouse cells. The mouse cells transfected with HPRT Utrecht showed no increase in HPRT activity; however, when the mouse cells were transfected with HPRT Yonago, the activity increased to 2.4% that of normal activity. The proliferative phenotypes of these cells in HAT medium and in medium containing 6-thioguanine were similar to those of skin fibroblasts from the patients. This series of studies confirmed that each of the two point mutations was responsible for the decreases in HPRT enzyme activity, and the proliferative phenotypes in HAT medium and medium containing 6-thioguanine.
MESH: Adolescence-; Base-Sequence; Cell-Line; Cells,-Cultured; Child-; DNA-analysis; DNA-Primers; Fibroblasts-; Gout-enzymology; Hypoxanthine-Phosphoribosyltransferase-metabolism; Japan-; Lesch-Nyhan-Syndrome-enzymology; Mice-; Molecular-Sequence-Data; Polymerase-Chain-Reaction; RNA,-Messenger-metabolism; Transfection-
MESH: *Gene-Expression-Regulation,-Enzymologic; *Gout-genetics; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Point-Mutation
TG: Animal; Case-Report; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Primers; RNA,-Messenger; DNA
AN: 94156348
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 39 of 122
TI: Expression of Escherichia coli beta-galactosidase and rat HPRT in the CNS of Macaca mulatta following adenoviral mediated gene transfer.
AU: Davidson-BL; Doran-SE; Shewach-DS; Latta-JM; Hartman-JW; Roessler-BJ
AD: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0680.
SO: Exp-Neurol. 1994 Feb; 125(2): 258-67
ISSN: 0014-4886
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli beta-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. Multiple analyses (including immunohistochemistry, histochemistry, transmission electron microscopy, RNA in situ hybridization, nucleotide pool analysis, and enzyme assay) confirmed efficient expression of beta-galactosidase and rat HPRT. Transgene expression was evident in both neurons and glia. Clinically, no evidence of meningitis or cerebritis was observed and no focal neurological deficits were detected in the animal. These preliminary studies indicate that recombinant adenovirus is capable of mediating high level transgene expression to the brains of higher order mammals.
MESH: Escherichia-coli-enzymology; Gene-Expression; Genetic-Vectors; Lac-Operon-physiology; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Macaca-mulatta; Rats-
MESH: *beta-Galactosidase-genetics; *Adenoviridae-genetics; *Caudate-Nucleus-physiology; *Escherichia-coli-genetics; *Gene-Transfer; *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: R01DK47968DKNIDDK
RN: EC 2.4.2.8; EC 3.2.1.23; 0
NM: Hypoxanthine-Phosphoribosyltransferase; beta-Galactosidase; Genetic-Vectors
AN: 94148048
UD: 9405
MEDLINE EXPRESS (R) 1991-1995 40 of 122
TI: Expression cloning of multiple human cDNAs that complement the phenotypic defects of ataxia-telangiectasia group D fibroblasts.
AU: Meyn-MS; Lu-Kuo-JM; Herzing-LB
AD: Department of Genetics, School of Medicine, Yale University, New Haven, CT 06510.
SO: Am-J-Hum-Genet. 1993 Dec; 53(6): 1206-16
ISSN: 0002-9297
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Ataxia-telangiectasia (A-T) is an inherited human disease of unknown etiology associated with neurologic degeneration, immune dysfunction, cancer risk, and genetic instability. A-T cells are sensitive to ionizing radiation and radiomimetic drugs, offering the possibility of cloning A-T genes by phenotypic complementation. We have used this sensitivity to isolate the first human cDNAs reported to complement A-T cells in culture. Complementation group D A-T fibroblasts were transfected with an episomal vector-based human cDNA library, approximately 610,000 resultant transformants were treated with the radiomimetic drug streptonigrin-resistant, and nine unrelated cDNAs were recovered from 29 surviving streptonigrin-resistant clones. Five cDNAs were mapped, but none localized to 11q23, the site of A-T complementation group A and C loci. Four of the mapped cDNAs conferred mutagen resistance to A-T D fibroblasts on secondary transfection. One cDNA was identified as a fragment of dek, a gene involved in acute myeloid leukemia. The dek cDNA fragment and pCAT4.5, a 4.5-kb cDNA that mapped to 17p11, independently complemented three different phenotypic abnormalities of A-T D fibroblasts (mutagen sensitivity, hyper-recombination, and radio-resistant DNA synthesis). The pCAT4.5 cDNA did not complement the mutagen sensitivity of an A-T group C fibroblast line, suggesting that it represents a candidate disease gene for group D A-T. Our results indicate that phenotypic complementation alone is insufficient evidence to prove that a candidate cDNA is an A-T disease gene. The complementing cDNAs may represent previously uncharacterized genes that function in the same pathway as does the A-T gene product(s) in the regulation of cellular responses to DNA damage.
MESH: Ataxia-Telangiectasia-pathology; Blotting,-Northern; Blotting,-Southern; Cell-Line,-Transformed; Cell-Survival-drug-effects; Cell-Survival-radiation-effects; Chromosome-Mapping; Cloning,-Molecular; DNA-isolation-and-purification; Fibroblasts-drug-effects; Fibroblasts-radiation-effects; Gene-Library; Genetic-Complementation-Test; Lesch-Nyhan-Syndrome-pathology; Phenotype-; RNA-analysis; Sequence-Analysis,-DNA; Streptonigrin-pharmacology; Transfection-; Transformation,-Genetic
MESH: *Ataxia-Telangiectasia-genetics; *Chromosomes,-Human,-Pair-17; *Fibroblasts-ultrastructure
TG: Human; Support,-Non-U.S.-Gov't
GS: dek; A-T; lacZ
PT: JOURNAL-ARTICLE
RN: 3930-19-6; 63231-63-0; 9007-49-2
NM: Streptonigrin; RNA; DNA
AN: 94070866
UD: 9403
MEDLINE EXPRESS (R) 1991-1995 41 of 122
TI: Self-injurious behaviour in retarded children: clinical phenomena and biological mechanisms.
AU: Buitelaar-JK
AD: Department of Child and Adolescent Psychiatry, University of Utrecht, The Netherlands.
SO: Acta-Paedopsychiatr. 1993; 56(2): 105-11
ISSN: 0936-7012
PY: 1993
LA: ENGLISH
CP: GERMANY
AB: Self-injurious behaviour (SIB) is a frequently occurring and serious problem in autistic and non-autistic retarded children. This paper first summarizes clinical knowledge on SIB. Attention is paid to the Lesch-Nyhan syndrome and Tourette's syndrome as examples of clinical syndromes that are particularly associated with SIB. Then animal models are reviewed that suggest the involvement of dopaminergic, opioidergic and serotonergic mechanisms in the pathophysiology of SIB. The putative biochemical models of SIB in humans are discussed and pharmacological interventions are briefly outlined.
MESH: Antipsychotic-Agents-pharmacology; Antipsychotic-Agents-therapeutic-use; Brain-drug-effects; Brain-physiopathology; Dopamine-metabolism; Dopamine-physiology; Fluphenazine-pharmacology; Fluphenazine-therapeutic-use; Lesch-Nyhan-Syndrome-physiopathology; Narcotics-metabolism; Receptors,-Dopamine-drug-effects; Receptors,-Dopamine-physiology; Receptors,-Serotonin-drug-effects; Self-Injurious-Behavior-drug-therapy; Self-Injurious-Behavior-physiopathology; Serotonin-metabolism; Serotonin-physiology; Tourette-Syndrome-physiopathology
MESH: *Lesch-Nyhan-Syndrome-complications; *Mental-Retardation-complications; *Self-Injurious-Behavior-complications; *Tourette-Syndrome-complications
TG: Female; Human; Male
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 0; 0; 50-67-9; 51-61-6; 69-23-8
NM: Antipsychotic-Agents; Narcotics; Receptors,-Dopamine; Receptors,-Serotonin; Serotonin; Dopamine; Fluphenazine
AN: 94182444
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 42 of 122
TI: Postnatal expression of hypoxanthine guanine phosphoribosyltransferase in the mouse brain.
AU: Ikeda-K; Iida-T; Nakagawa-S
AD: Department of Applied Biological Science, College of Agriculture and Veterinary Medicine, Nihon University, Kanagawa, Japan.
SO: Enzyme-Protein. 1993; 47(2): 65-72
ISSN: 1019-6773
PY: 1993
LA: ENGLISH
CP: SWITZERLAND
AB: The distributional and activity changes of hypoxanthine guanine phosphoribosyltransferase (HGPRT) were investigated in the developing mouse brain. The HGPRT activity level was low at birth, increased rapidly during the first 7 days of life, and underwent a gradual increase thereafter to the mature level. Polyclonal antibody against HGPRT purified from mouse brain was prepared for immunohistochemical demonstration of the enzyme during brain development. In the cerebellum, part of the Purkinje cells was consistently immunostained throughout growth, and the presence of HGPRT was observed in the dendrites of mature Purkinje cells. The most dominant change in HGPRT localization was observed in the hippocampus. Little HGPRT was detectable in the newborn mouse hippocampus. At postnatal day 7, cytoplasmic HGPRT appeared sporadically in the granular cells independently of the region of the hippocampus. The number of positive immunoreactive cells increased with growth, and the dendrites of granular cells were also immunostained on postnatal day 28. Further immunostaining was noted in the granule cells of the dentate gyrus on postnatal day 35. The above results suggest that HGPRT may play an important role in the developing hippocampus. Further investigations of the HGPRT in the human hippocampus may help to clarify the mechanism underlying the neurological disorders encountered in the Lesch-Nyhan syndrome.
MESH: Aging-; Animals,-Newborn; Cerebellum-enzymology; Hippocampus-enzymology; Immunohistochemistry-; Lesch-Nyhan-Syndrome-etiology; Mice-; Mice,-Inbred-Strains; Purkinje-Cells-enzymology; Tissue-Distribution
MESH: *Brain-enzymology; *Hypoxanthine-Phosphoribosyltransferase-isolation-and-purification
TG: Animal
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 94251293
UD: 9409
MEDLINE EXPRESS (R) 1991-1995 43 of 122
TI: Molecular genetic study of a Japanese family with Lesch-Nyhan syndrome: a point mutation at the consensus region of RNA splicing (HPRTKeio).
AU: Yamada-Y; Goto-H; Tamura-S; Ogasawara-N
AD: Department of Genetics, Aichi Prefectural Colony, Japan.
SO: Jpn-J-Hum-Genet. 1993 Dec; 38(4): 413-9
ISSN: 0916-8478
PY: 1993
LA: ENGLISH
CP: JAPAN
AB: Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A single nucleotide substitution of G to T at the 3'-end of intron 3 in the splicing consensus region has been identified in one allele of the HPRT gene from a mother predicted to be a heterozygous Lesch-Nyhan carrier. Utilizing a BfaI restriction site which was lost in the mutation as an indicator, family study showed that the mother and her only daughter were heterozygotes but the mother's sister did not have the mutant allele. The mutation generated splicing error and resulted in two types of abnormal mRNA. The major altered mRNA, named Type I, skipped the exon 4 and is predicted to produce a protein deleted of 22 amino acid residues. The other, Type II, having a 9-bp deletion at the 5'-end of exon 4, can result in a protein lacking 3 amino acids, from codon 107 to 109.
MESH: Base-Sequence; DNA-Primers; Hypoxanthine-Phosphoribosyltransferase-deficiency; Japan-; Lesch-Nyhan-Syndrome-ethnology; Molecular-Sequence-Data
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Point-Mutation; *RNA-Splicing
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Primers
AN: 94242975
UD: 9408
MEDLINE EXPRESS (R) 1991-1995 44 of 122
TI: Molecular analysis of the mutations in five unrelated patients with the Lesch Nyhan syndrome.
AU: Marcus-S; Christensen-E; Malm-G
AD: Environmental Medicine Unit, Karolinska Institutet, Huddinge, Sweden.
SO: Hum-Mutat. 1993; 2(6): 473-7
ISSN: 1059-7794
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: We have identified the mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in five patients with the Lesch Nyhan syndrome (LN) by direct sequencing of hprt cDNA and genomic DNA. Three of the mutations affect splicing of exons 1, 2, and 9, respectively, while two are missense mutations in exons 3 and 8. All 5 mutations result in profound hprt deficiency as measured in fibroblast lysates. However, small differences in the clinical phenotype are seen between the patients. All these mutations are unique and have not been reported previously.
MESH: Adolescence-; Adult-; Child-; Child,-Preschool; Exons-; Infant-; Lesch-Nyhan-Syndrome-enzymology; Phenotype-; RNA-Splicing
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
GS: hprt
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 94154734
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 45 of 122
TI: Lesch-Nyhan syndrome.
AU: Kulkarni-ML; Sureshkumar-C; George-VG
AD: Department of Pediatrics, J.J.M. Medical College, Davangere, Karnataka.
SO: Indian-Pediatr. 1993 Apr; 30(4): 537-40
ISSN: 0019-6061
PY: 1993
LA: ENGLISH
CP: INDIA
MESH: Child,-Preschool; Fatal-Outcome; Infant-; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics
MESH: *Lesch-Nyhan-Syndrome
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 94117140
UD: 9404
MEDLINE EXPRESS (R) 1991-1995 46 of 122
TI: HPLC determination of oxidized and reduced pyridine coenzymes in human erythrocytes.
AU: Micheli-V; Simmonds-HA; Bari-M; Pompucci-G
AD: Dipartimento di Biologia Molecolare, Universita di Siena, Italy.
SO: Clin-Chim-Acta. 1993 Oct 29; 220(1): 1-17
ISSN: 0009-8981
PY: 1993
LA: ENGLISH
CP: NETHERLANDS
AB: The nucleotide concentrations in acid and alkaline erythrocyte extracts have been measured by RP-HPLC in healthy controls and in patients bearing different inherited disorders, with altered erythrocyte NAD(P) levels. The objective was the simultaneous determination of the nucleotide profile and of the oxidative state of pyridine coenzymes by the most suitable extraction method. Both alkaline and acid extractions were necessary to obtain the complete pattern, due to defective recovery of the oxidized or reduced coenzymes, respectively, during the extraction procedures. Purine nucleotide quantification seemed to be reliable by all methods. High NADP+ levels were confirmed in two glucose-6-phosphate dehydrogenase deficient patients, coupled with raised NAD levels, lowered NADPH/NADP+ ratio and increased NADH/NAD+ ratio. Higher NAD+ and normal or lower NADH/NAD+ ratios were found in two hypoxanthine-phosphoribosyltransferase deficient patients, while a patient with superactive phosphoribosylpyrophosphate synthetase showed a decreased NADH level in addition to the low NAD+ level previously found.
MESH: Chromatography,-High-Pressure-Liquid; Glycogen-Storage-Disease-Type-I-blood; Lesch-Nyhan-Syndrome-blood; NAD-isolation-and-purification; NADP-isolation-and-purification; Oxidation-Reduction; Purine-Nucleoside-Phosphorylase-deficiency; Ribose-Phosphate-Pyrophosphokinase-metabolism
MESH: *Erythrocytes-chemistry; *NAD-blood; *NADP-blood
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.1; EC 2.7.6.1; 53-59-8; 53-84-9
NM: Purine-Nucleoside-Phosphorylase; Ribose-Phosphate-Pyrophosphokinase; NADP; NAD
AN: 94116162
UD: 9404
MEDLINE EXPRESS (R) 1991-1995 47 of 122
TI: Decreased 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in patients with Lesch-Nyhan syndrome.
AU: Imamura-A; Yamanouchi-H; Arima-M
AD: Division of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan.
SO: Brain-Dev. 1993 Sep-Oct; 15(5): 381-3
ISSN: 0387-7604
PY: 1993
LA: ENGLISH
CP: NETHERLANDS
AB: The coagulation abnormality in patients with Lesch-Nyhan syndrome (LNS) prompted us to examine 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), a stable metabolite of prostacyclin (PGI2). Plasma levels of 6-keto PGF1 alpha were significantly low in 4 patients with LNS, but they were elevated after discontinuation of allopurinol. Other indicators of coagulation and fibrinolysis systems did not change after the discontinuation of allopurinol. PGI2 prevents the production of superoxide which is formed after cerebral ischemia. The potential source of superoxide is xanthine oxidase which is inhibited by allopurinol. It is assumed that plasma PGI2 increased in response to formed superoxide because xanthine oxidase inhibition was abolished after discontinuation of allopurinol.
MESH: beta-Thromboglobulin-metabolism; Adolescence-; Adult-; Allopurinol-adverse-effects; Allopurinol-therapeutic-use; Blood-Coagulation; Child-; Fibrinopeptides-A-metabolism; Kidney-Function-Tests; Lesch-Nyhan-Syndrome-drug-therapy; Platelet-Factor-4-metabolism; Superoxides-metabolism
MESH: *Lesch-Nyhan-Syndrome-blood; *6-Ketoprostaglandin-F1-alpha-blood
TG: Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 0; 11062-77-4; 315-30-0; 37270-94-3; 58962-34-8
NM: beta-Thromboglobulin; Fibrinopeptides-A; Superoxides; Allopurinol; Platelet-Factor-4; 6-Ketoprostaglandin-F1-alpha
AN: 94106757
UD: 9404
MEDLINE EXPRESS (R) 1991-1995 48 of 122
TI: [Movement disorders in miscellaneous disorders--inherited metabolic diseases]
AU: Mizuguchi-M; Kamoshita-S
AD: Department of Pediatrics, Faculty of Medicine, University of Tokyo.
SO: Nippon-Rinsho. 1993 Nov; 51(11): 2919-23
ISSN: 0047-1852
PY: 1993
LA: JAPANESE; NON-ENGLISH
CP: JAPAN
AB: A variety of inheritable metabolic disorders produce movement disorders. A lists of conditions associated with tremor, athetosis, chorea, dystonia and myoclonus are presented as a guide for the differential diagnosis of such abnormal involuntary movements. The list includes aminoacidopathies, lipidoses, mucopolysaccharidoses, mucolipidoses, organic acidemias, mitochondrial cytopathies and disorders of carbohydrate, purine, and metal metabolism. Clinical, pathological and biochemical features of movement disorders of three typical examples, Wilson's disease, Lesch-Nyhan syndrome and glutaric acidemia type 1, are described.
MESH: Diagnosis,-Differential; English-Abstract; Hepatolenticular-Degeneration-complications; Hepatolenticular-Degeneration-physiopathology; Lesch-Nyhan-Syndrome-complications; Lesch-Nyhan-Syndrome-physiopathology; Movement-Disorders-diagnosis
MESH: *Metabolism,-Inborn-Errors-complications; *Movement-Disorders-etiology
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 94104100
UD: 9404
MEDLINE EXPRESS (R) 1991-1995 49 of 122
TI: In vivo mutation at the human HPRT locus.
AU: Cariello-NF; Skopek-TR
AD: Pathology Department, University of North Carolina, Chapel Hill.
SO: Trends-Genet. 1993 Sep; 9(9): 322-6
ISSN: 0168-9525
PY: 1993
LA: ENGLISH
CP: ENGLAND
AB: The molecular nature of mutations that arise in vivo at the human hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus can be determined. A wide variety of such mutations can be detected, including large and small deletions, frameshift mutations and single-base substitutions, as well as alterations that cause aberrant mRNA splicing. Here, we review the available information on mutations at this locus.
MESH: Adult-; Cells,-Cultured; DNA-Mutational-Analysis; Exons-; Frameshift-Mutation; Gout-genetics; Infant,-Newborn; Lesch-Nyhan-Syndrome-genetics; Point-Mutation; RNA-Splicing; Sequence-Deletion; Smoking-genetics; T-Lymphocytes; X-Chromosome
MESH: *Genes,-Structural; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Mutation-
TG: Human
GS: HPRT
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 94054664
UD: 9402
MEDLINE EXPRESS (R) 1991-1995 50 of 122
TI: Lesch-Nyhan syndrome and the lower lip guard.
AU: Evans-J; Sirikumara-M; Gregory-M
AD: Department of Oral and Maxillofacial Surgery, the Royal Gwent Hospital, Newport, South Wales, U.K.
SO: Oral-Surg-Oral-Med-Oral-Pathol. 1993 Oct; 76(4): 437-40
ISSN: 0030-4220
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Lesch-Nyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and factitious oral lesions, which cause immense difficulties in its management. A case of an 11-year-old boy, the elder of two siblings with this condition, who had severe self-inflicted injuries to oral and perioral tissues is presented highlighting the different treatment modalities considered. A tailor-made lipguard proved to provide the best cosmetic result short term.
MESH: Child-
MESH: *Lesch-Nyhan-Syndrome-physiopathology; *Lip-injuries; *Mouth-Protectors; *Self-Mutilation-prevention-and-control
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 94051159
UD: 9402
SB: DENTAL
MEDLINE EXPRESS (R) 1991-1995 51 of 122
TI: Fluorescent approaches to diagnosis of Lesch-Nyhan syndrome and quantitative analysis of carrier status.
AU: Mansfield-ES; Blasband-A; Kronick-MN; Wrabetz-L; Kaplan-P; Rappaport-E; Sartore-M; Parrella-T; Surrey-S; Fortina-P
AD: Applied Biosystems, Inc., Foster City, CA.
SO: Mol-Cell-Probes. 1993 Aug; 7(4): 311-24
ISSN: 0890-8508
PY: 1993
LA: ENGLISH
CP: ENGLAND
AB: Lesch-Nyhan syndrome is an X-linked recessive disorder caused by molecular defects within the HPRT gene. Deletional forms of this syndrome, most of which are inherited, account for 15% of the cases. In addition, a large percentage of cases are due to de novo point mutations. We have used complementary fluorescence-based PCR assays to analyse disease-causing mutations in three unrelated families: (1) inheritance of dye-labelled PCR products of linked polymorphic loci mapping within and flanking the HPRT gene; (2) dye-labelled exon dosage analysis and (3) automated fluorescence-based DNA sequence analysis. Our results using fluorescent, dye-tagged PCR products show that inheritance of two polymorphic small tandem repeats, HPRTB [AGAT]n, mapping within intron 3 of the HPRT gene, and the CA-repeat at DXS294 can be used to establish linkage to the disease. In addition, we modified a previously described PCR protocol to use fluorescent dye-labelled oligoprimers and an ABI Gene Scanner in order to rapidly quantitate deletional forms of Lesch-Nyhan syndrome. Quantitative PCR analysis of individual exons followed by dosage analysis confirmed a deletion encompassing exon 9. A similar approach was used to confirm a previously described HPRT gene duplication involving exons 2 and 3. In this analysis, we co-amplified the HPRTB [AGAT]n and HUMARA [AGC]n repeats and confirmed increased exon dosage in carriers for the duplication. DNA sequence analysis remains the method of choice for delineating new disease-causing mutations, most of which are non-deletional forms of Lesch-Nyhan syndrome. We have also used a cycle-sequencing strategy employing dye-labelled dideoxy terminators and a laser-activated, fluorescence-emission DNA sequencer in order to define carrier status in 10 family members at risk for Lesch-Nyhan syndrome due to a splice donor mutation in intron 7. Our DNA sequence analyses corroborate small tandem repeat (STR) inheritance patterns in this family. Multiple fluorescence-based strategies should facilitate rapid diagnosis of the various Lesch-Nyhan disease-causing mutations.
MESH: Adolescence-; Adult-; Base-Sequence; DNA-Primers; Genes,-Reiterated; Introns-genetics; Lesch-Nyhan-Syndrome-genetics; Linkage-Genetics; Molecular-Sequence-Data; Pedigree-; Polymorphism-Genetics; Repetitive-Sequences,-Nucleic-Acid-genetics; Sequence-Analysis,-DNA; Sequence-Deletion
MESH: *Heterozygote-; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-diagnosis; *Point-Mutation-genetics; *Polymerase-Chain-Reaction-methods
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Primers
AN: 94049854
UD: 9402
MEDLINE EXPRESS (R) 1991-1995 52 of 122
TI: Germ-line gene modification and disease prevention: some medical and ethical perspectives.
AU: Wivel-NA; Walters-L
AD: Office of Recombinant DNA Activities, National Institutes of Health, Bethesda, MD 20892.
SO: Science. 1993 Oct 22; 262(5133): 533-8
ISSN: 0036-8075
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease.
MESH: Eye-Neoplasms-prevention-and-control; Lesch-Nyhan-Syndrome-prevention-and-control; Leukodystrophy,-Metachromatic-prevention-and-control; Retinoblastoma-prevention-and-control; Tay-Sachs-Disease-prevention-and-control
MESH: *Blastocyst-; *Ethics,-Medical; *Gene-Therapy; *Gene-Transfer; *Germ-Cells; *Hereditary-Diseases-prevention-and-control
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 94024006
UD: 9401
MEDLINE EXPRESS (R) 1991-1995 53 of 122
TI: Duplication in the hypoxanthine phosphoribosyl-transferase gene caused by Alu-Alu recombination in a patient with Lesch Nyhan syndrome.
AU: Marcus-S; Hellgren-D; Lambert-B; Fallstrom-SP; Wahlstrom-J
AD: Environmental Medicine Unit, Karolinska Institutet, CNT/Novum, Huddinge, Sweden.
SO: Hum-Genet. 1993 Jan; 90(5): 477-82
ISSN: 0340-6717
PY: 1993
LA: ENGLISH
CP: GERMANY
AB: We have determined the structure, at the nucleotide sequence level, of a duplication in the hprt gene in a patient with Lesch-Nyhan syndrome (LN). The duplication extends over exons 7 and 8 and approximately 1.8 kb of the surrounding hprt sequence. The duplication junction is localized within two Alu sequences and has apparently been generated by unequal homologous recombination. This is the second reported case of a partial duplication of the hprt gene in an LN patient, and the first that involves an Alu-Alu recombination.
MESH: Base-Sequence; Blotting,-Southern; Crossing-Over-Genetics; DNA-Mutational-Analysis; DNA,-Single-Stranded; Exons-; Frameshift-Mutation; Infant-; Introns-; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Sequence-Homology,-Nucleic-Acid
MESH: *DNA-Insertion-Elements; *Genes,-Reiterated; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Repetitive-Sequences,-Nucleic-Acid
TG: Case-Report; Human; Male; Support,-Non-U.S.-Gov't
GS: hprt
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Insertion-Elements; DNA,-Single-Stranded
AN: 93154711
UD: 9305
SI: GENBANK/S54071; GENBANK/M98868; GENBANK/S70572; GENBANK/S70573; GENBANK/L13238; GENBANK/L13296; GENBANK/L13297; GENBANK/L14001; GENBANK/L14002; GENBANK/L14003
MEDLINE EXPRESS (R) 1991-1995 54 of 122
TI: Characterization of the alterations in purine nucleotide metabolism in hypoxanthine-guanine phosphoribosyltransferase-deficient rat neuroma cell line.
AU: Zoref-Shani-E; Bromberg-Y; Brosh-S; Sidi-Y; Sperling-O
AD: Department of Chemical Pathology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
SO: J-Neurochem. 1993 Aug; 61(2): 457-63
ISSN: 0022-3042
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: A rat neuroma cell line (B103 4C), deficient of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), was utilized as a model tissue in search for the biochemical basis of the Lesch-Nyhan syndrome (LNS). The HGPRT-deficient neurons exhibited the following properties: an almost complete absence of uptake of guanine and of hypoxanthine into intact cell nucleotides (0.92% and 0.69% of normal, respectively); a significant increase in the availability of 5'-phosphoribosyl-1-pyrophosphate; a three- to fourfold acceleration of the rate of de novo nucleotide synthesis; a normal excretion of xanthine, but 15-fold increase in the excretion of hypoxanthine into the culture media; a normal cellular purine nucleotide content, including the absence of 5-amino-4-imidazole carboxamide nucleotides (Z-nucleotides), but enhanced turnover of adenine nucleotides (loss of 86% of the radioactivity of the prelabeled pool in 24 h, in comparison to 73% in the normal line), and an elevated UTP content. The results suggest that, under physiological conditions, guanine salvage does not occur in the normal neurons, but that hypoxanthine salvage is of great importance in the homeostasis of the adenine nucleotide pool. The finding of the normal profile of purine nucleotides in the HGPRT-deficient neurons indicates that the lack of hypoxanthine salvage is adequately compensated by the enhanced de novo nucleotide synthesis. These results did not furnish evidence in support of the possibility that GTP or ATP depletion, or Z-nucleotide accumulation, occurs in HGPRT-deficient neurons and that these are etiological factors causing the neurological abnormalities in LNS.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Adenine-metabolism; Adenine-Nucleotides-metabolism; Formic-Acids-metabolism; Guanine-metabolism; Hypoxanthines-metabolism; Lesch-Nyhan-Syndrome-metabolism; Neuroma-metabolism; Rats-; Tumor-Cells,-Cultured; Xanthines-metabolism
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Purine-Nucleotides-metabolism
TG: Animal; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0; 0; 0; 0; 64-18-6; 68-94-0; 69-89-6; 73-24-5; 73-40-5
NM: Hypoxanthine-Phosphoribosyltransferase; Adenine-Nucleotides; Formic-Acids; Hypoxanthines; Purine-Nucleotides; Xanthines; formic-acid; hypoxanthine; xanthine; Adenine; Guanine
AN: 93329409
UD: 9310
MEDLINE EXPRESS (R) 1991-1995 55 of 122
TI: Screening for molecular pathologies in Lesch-Nyhan syndrome.
AU: Boyd-M; Lanyon-WG; Connor-JM
AD: University Department of Medical Genetics, Duncan Guthrie Institute, Glasgow, United Kingdom.
SO: Hum-Mutat. 1993; 2(2): 127-30
ISSN: 1059-7794
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Heteroduplex detection by hydrolink gel electrophoresis was performed to screen for small mutations in 12 Lesch-Nyhan syndrome families with characterised molecular pathology which included nine point mutations, two small deletions, and a 1-bp insertion. This modified protocol for heteroduplex detection by hydrolink gel electrophoresis detected all 12 of these mutations and was utilised to rapidly determine the carrier status of females from affected families. On the basis of these results this approach appears to be a rapid and reliable screening method for point mutations in addition to small length mutations and for carrier detection in Lesch-Nyhan syndrome.
MESH: Electrophoresis-; Evaluation-Studies; Heterozygote-Detection-methods; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-enzymology; Nucleic-Acid-Heteroduplexes-isolation-and-purification; Point-Mutation; Polymerase-Chain-Reaction; Sequence-Deletion
MESH: *DNA-Mutational-Analysis-methods; *Lesch-Nyhan-Syndrome-genetics; *Nucleic-Acid-Heteroduplexes-genetics
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; Nucleic-Acid-Heteroduplexes
AN: 93306306
UD: 9310
MEDLINE EXPRESS (R) 1991-1995 56 of 122
TI: Identification of two new nucleotide mutations (HPRTUtrecht and HPRTMadrid) in exon 3 of the human hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene.
AU: Bouwens-Rombouts-AG; van-den-Boogaard-MJ; Puig-JG; Mateos-FA; Hennekam-RC; Tilanus-MG
AD: Diagnostic DNA Laboratory, University Hospital, Utrecht, The Netherlands.
SO: Hum-Genet. 1993 Jun; 91(5): 451-4
ISSN: 0340-6717
PY: 1993
LA: ENGLISH
CP: GERMANY
AB: Mutations in the X-linked hypoxanthine-guanine phosphoribosyl transferase gene (HPRT) result in deficiencies of HPRT enzyme activity, which may cause either a severe form of gout or Lesch-Nyhan syndrome depending on the residual enzyme activity. Mutations leading to these diseases are heterogeneous and include DNA base substitutions, DNA deletions, DNA base insertions and errors in RNA splicing. Identification of mutations has been performed at the RNA and DNA level. Sequencing genomic DNA of the HPRT gene offers the possibility of direct diagnostic analysis independent on the expression of the mature HPRT mRNA. We describe a Dutch and a Spanish family, in which the Lesch-Nyhan syndrome and a severe partial HPRT-deficient phenotype, respectively, were diagnosed. Direct sequencing of the exons coding for the HPRT gene was performed in both families. Two new exon 3 mutations have been identified. At position 16676, the normally present G was substituted by an A in the Dutch kindred (HPRTUtrecht), and led to an arginine for glycine change at residue 70. At position 16680, the G was substituted by a T in the Spanish family (HPRTMadrid); this substitutes a valine for glycine at residue 71. These new mutations are located within one of the clusters of hotspots in exon 3 of the HPRT gene in which HPRTYale and HPRTNew Haven have previously been identified.
MESH: Amino-Acid-Sequence; Arginine-genetics; Base-Sequence; DNA-Mutational-Analysis; Exons-; Glycine-genetics; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Netherlands-; Pedigree-; Spain-; Valine-genetics
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Point-Mutation
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 56-40-6; 7004-03-7; 7004-12-8
NM: Hypoxanthine-Phosphoribosyltransferase; Glycine; Valine; Arginine
AN: 93300482
UD: 9309
MEDLINE EXPRESS (R) 1991-1995 57 of 122
TI: Brain purines in a genetic mouse model of Lesch-Nyhan disease.
AU: Jinnah-HA; Page-T; Friedmann-T
AD: Department of Neurosciences and Pediatrics, University of California, San Diego School of Medicine, La Jolla.
SO: J-Neurochem. 1993 Jun; 60(6): 2036-45
ISSN: 0022-3042
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Mice carrying a mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) have recently been produced to provide an animal model for Lesch-Nyhan disease. The current studies were conducted to characterize the consequences of the mutation on the expression of HPRT and to characterize potential changes in brain purine content in these mutants. Our results indicate that the mutant animals have no detectable HPRT-immunoreactive material on western blots and no detectable HPRT enzyme activity in brain tissue homogenates, confirming that they are completely HPRT deficient (HPRT-). Despite the absence of HPRT-mediated purine salvage, the animals have apparently normal brain purine content. However, de novo purine synthesis, as measured by [14C]formate incorporation into brain purines, is accelerated four- to fivefold in the mutant animals. This increase in the synthesis of purines may protect the HPRT- mice from potential depletion of brain purines despite complete impairment of HPRT-mediated purine salvage.
MESH: Blotting,-Western; Brain-enzymology; Chromatography,-Affinity; Disease-Models,-Animal; Electrophoresis,-Polyacrylamide-Gel; Hypoxanthine-Phosphoribosyltransferase-genetics; Hypoxanthine-Phosphoribosyltransferase-isolation-and-purification; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Mice-; Mice,-Inbred-C57BL; Mice,-Mutant-Strains; Molecular-Weight; Organ-Specificity
MESH: *Adenine-Nucleotides-metabolism; *Brain-metabolism; *Hypoxanthine-Phosphoribosyltransferase-metabolism; *Lesch-Nyhan-Syndrome-metabolism; *Purines-metabolism
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
GS: HPRT
PT: JOURNAL-ARTICLE
CN: HD20034HDNICHD
RN: EC 2.4.2.8; 0; 0
NM: Hypoxanthine-Phosphoribosyltransferase; Adenine-Nucleotides; Purines
AN: 93260442
UD: 9308
MEDLINE EXPRESS (R) 1991-1995 58 of 122
TI: Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice.
AU: Wu-CL; Melton-DW
AD: Institute of Cell and Molecular Biology, Edinburgh University, Scotland.
SO: Nat-Genet. 1993 Mar; 3(3): 235-40
ISSN: 1061-4036
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan syndrome and the evaluation of novel therapies.
MESH: Adenine-analogs-and-derivatives; Adenine-metabolism; Adenine-pharmacology; Adenine-Phosphoribosyltransferase-metabolism; Caffeine-pharmacology; Cell-Division-drug-effects; Cells,-Cultured; Disease-Models,-Animal; Embryo-; Hypoxanthines-metabolism; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-physiopathology; Mice-; Mice,-Mutant-Strains; Self-Injurious-Behavior; Stem-Cells-cytology; Stem-Cells-drug-effects; Stem-Cells-enzymology; Thymidine-metabolism
MESH: *Brain-metabolism; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-enzymology; *Purines-metabolism
TG: Animal; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.7; EC 2.4.2.8; 0; 0; 2715-68-6; 50-89-5; 58-08-2; 68-94-0; 73-24-5
NM: Adenine-Phosphoribosyltransferase; Hypoxanthine-Phosphoribosyltransferase; Hypoxanthines; Purines; 9-ethyladenine; Thymidine; Caffeine; hypoxanthine; Adenine
AN: 93251042
UD: 9308
MEDLINE EXPRESS (R) 1991-1995 59 of 122
TI: Parkinson's disease and the adaptive capacity of the nigrostriatal dopamine system: possible neurochemical mechanisms.
AU: Hornykiewicz-O
AD: Institute of Biochemical Pharmacology, University of Vienna, Austria.
SO: Adv-Neurol. 1993; 60: 140-7
ISSN: 0091-3952
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
MESH: Glutamine-physiology; Huntington's-Disease-physiopathology; Lesch-Nyhan-Syndrome-physiopathology; Malignant-Hyperthermia-physiopathology; Neurons-physiology; Receptors,-Glutamate-physiology
MESH: *Corpus-Striatum-physiopathology; *Dopamine-physiology; *Parkinson-Disease-physiopathology; *Receptors,-Dopamine-physiology; *Substantia-Nigra-physiopathology
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 51-61-6; 6899-04-3
NM: Receptors,-Dopamine; Receptors,-Glutamate; Dopamine; Glutamine
AN: 93128013
UD: 9304
MEDLINE EXPRESS (R) 1991-1995 60 of 122
TI: A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease.
AU: Fujimori-S; Tagaya-T; Kamatani-N; Akaoka-I
AD: Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
SO: Hum-Genet. 1992 Dec; 90(4): 385-8
ISSN: 0340-6717
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: Lesch-Nyhan syndrome caused by a complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) is the result of a heterogeneous group of germ line mutations. Identification of each mutant gene provides valuable information as to the type of mutation that occurs spontaneously. We report here a newly identified HPRT mutation in a Japanese patient with Lesch-Nyhan syndrome. This gene, designated HPRT Tokyo, had a single nucleotide change from G to A, as identified by sequencing cDNA amplified by the polymerase chain reaction. Allele specific oligonucleotide hybridization analysis using amplified genomic DNA showed that the mutant gene was transmitted from the maternal germ line. This mutation would lead to an amino acid substitution of Asp for Gly at the amino acid position 140 located within the putative 5-phosphoribosyl-1-pyrophosphate (PRPP) binding region. Missense mutations in human HPRT deficient patients thus far reported tend to accumulate in this functionally active region. However, a comparison of the data suggested that both missense and synonymous mutations can occur at any coding sequence of the human germ line HPRT gene, but that a limited percentage of all the missense mutations cause disease. The probability that a mutation will cause disease tends to be higher when the missense mutation is within a functionally important sequence.
MESH: Amino-Acid-Sequence; Base-Sequence; Binding-Sites; Blotting,-Western; Cell-Line; DNA,-Single-Stranded; Hypoxanthine-Phosphoribosyltransferase-genetics; Hypoxanthine-Phosphoribosyltransferase-metabolism; Japan-; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Sequence-Homology,-Amino-Acid
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-genetics; *Mutation-; *Phosphoribosyl-Pyrophosphate-metabolism
TG: Female; Human; Male
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 7540-64-9
NM: Hypoxanthine-Phosphoribosyltransferase; DNA,-Single-Stranded; Phosphoribosyl-Pyrophosphate
AN: 93131267
UD: 9304
MEDLINE EXPRESS (R) 1991-1995 61 of 122
TI: Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.
AU: Lambert-B; Marcus-S; Andersson-B; Hou-SM; Steen-AM; Hellgren-D
AD: Environmental Medicine Unit, Karolinska Institutet, Huddinge, Sweden.
SO: Pharmacogenetics. 1992 Dec; 2(6): 329-36
ISSN: 0960-314X
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens.
MESH: Amino-Acid-Sequence; Base-Sequence; Conserved-Sequence; DNA-genetics; DNA-Mutational-Analysis; Evolution-; Gout-enzymology; Gout-genetics; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Plasmodium-falciparum-enzymology; Plasmodium-falciparum-genetics; Schistosoma-mansoni-enzymology; Schistosoma-mansoni-genetics
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Animal; Comparative-Study; Human; Support,-Non-U.S.-Gov't
GS: hprt
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 93306361
UD: 9310
MEDLINE EXPRESS (R) 1991-1995 62 of 122
TI: Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency.
AU: Sege-Peterson-K; Chambers-J; Page-T; Jones-OW; Nyhan-WL
AD: Department of Pediatrics, University of California, San Diego, La Jolla 92093.
SO: Hum-Mol-Genet. 1992 Sep; 1(6): 427-32
ISSN: 0964-6906
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: The Lesch-Nyhan disease is caused by an almost complete lack of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Partial HPRT-deficiency, associated with less severe phenotype, has also been identified. We have characterized mutations occurring in HPRT cDNA isolated from patients with HPRT-deficiency with an emphasis on examining the more unusual partial variants of HPRT-deficiency. HPRT cDNA was amplified by PCR, cloned and analyzed by automated DNA sequence analysis. Twenty-two, unrelated individuals with HPRT deficiency were studied including eight classic Lesch-Nyhan patients and fourteen patients representing the different groups of partial HPRT deficiency. We found a diverse pattern of mutations with point mutations accounting for the majority of abnormal HPRT genes. Nonsense mutations and exon deletions were only found in HPRT cDNA isolated from classic Lesch-Nyhan patients. Mutations associated with partial HPRT-deficiency were frequently located in the amino terminal part of the molecule. A CpG mutational hot spot was identified at the position for Arg-51 in the HPRT protein. Two hyperuricemic patients exhibited unusual splice site mutations: in one this led to the creation of an additional exon in the HPRT gene and in the other part of exon 6 was missing in a subpopulation of the transcripts, producing the effect of a dominant, negative mutation.
MESH: Amino-Acid-Sequence; Base-Sequence; Cells,-Cultured; Cloning,-Molecular; DNA-genetics; DNA-isolation-and-purification; Exons-; Fibroblasts-enzymology; Hypoxanthine-Phosphoribosyltransferase-metabolism; Lesch-Nyhan-Syndrome-enzymology; Lymphocyte-Transformation; Lymphocytes-immunology; Lymphocytes-physiology; Molecular-Sequence-Data; Oligodeoxyribonucleotides-; Phenotype-; Polymerase-Chain-Reaction-methods; Skin-enzymology; Skin-pathology
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-; *Point-Mutation; *Variation-Genetics
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD2304203HDNICHD; RR00827RRNCRR
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; Oligodeoxyribonucleotides; DNA
AN: 93250785
UD: 9308
SI: GENBANK/S60300; GENBANK/X64597; GENBANK/X64598; GENBANK/X64599; GENBANK/M88632; GENBANK/M88633; GENBANK/M88634; GENBANK/M88635; GENBANK/M88636; GENBANK/M88637
MEDLINE EXPRESS (R) 1991-1995 63 of 122
TI: Elevated fibrinopeptide A (FPA) in patients with Lesch-Nyhan syndrome.
AU: Imamura-A; Yamanouchi-H; Kurokawa-T; Arima-M
AD: Division of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan.
SO: Brain-Dev. 1992 Nov; 14(6): 424-5
ISSN: 0387-7604
PY: 1992
LA: ENGLISH
CP: JAPAN
AB: The detection of elevated fibrinopeptide A (FPA) level in a patient with the Lesch-Nyhan syndrome complicated with cerebral infarction prompted us to examine FPA level in 3 other patients with the syndrome. FPA level significantly increased in all patients. Fibrinopeptide B beta 15-42 (FPB beta 15-42) level was increased in two, and both beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) levels were elevated in one patient. These results suggest coagulation abnormalities in patients with Lesch-Nyhan syndrome.
MESH: Adolescence-; Adult-; Blood-Coagulation-Factors-analysis; Child-
MESH: *Fibrinopeptides-A-analysis; *Lesch-Nyhan-Syndrome-blood
TG: Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 0
NM: Blood-Coagulation-Factors; Fibrinopeptides-A
AN: 93151417
UD: 9305
MEDLINE EXPRESS (R) 1991-1995 64 of 122
TI: Serotonin-GABA treatment is hypothesized for self-injury in Lesch-Nyhan syndrome [published erratum appears in Med Hypotheses 1993 Feb;40(2):142]
AU: Gedye-A
SO: Med-Hypotheses. 1992 Aug; 38(4): 325-8
ISSN: 0306-9877
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: The self-injurious movements of Lesch-Nyhan patients are considered extremely severe and currently intractable. Lesch-Nyhan syndrome is a genetic disorder of purine metabolism resulting in several abnormalities, one of which is elevated levels of xanthine. The author reasons that elevated plasma xanthine sets off a chain of events that produce excessive endogenous convulsants and diminished endogenous anticonvulsants. Treatment is proposed for self-injury in Lesch-Nyhan that entails reducing production of two endogenous convulsants (kynurenine and quinolinic acid) and enhancing two endogenous anticonvulsants (serotonin and gamma aminobutyric acid).
MESH: Drug-Therapy,-Combination; GABA-metabolism; Kynurenine-antagonists-and-inhibitors; Kynurenine-biosynthesis; Lesch-Nyhan-Syndrome-complications; Lesch-Nyhan-Syndrome-metabolism; Self-Injurious-Behavior-etiology; Serotonin-metabolism
MESH: *Baclofen-administration-and-dosage; *Lesch-Nyhan-Syndrome-drug-therapy; *Self-Injurious-Behavior-drug-therapy; *Serotonin-administration-and-dosage
TG: Human; Male
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 1134-47-0; 343-65-7; 50-67-9; 56-12-2
NM: Baclofen; Kynurenine; Serotonin; GABA
AN: 93148870
UD: 9305
MEDLINE EXPRESS (R) 1991-1995 65 of 122
TI: A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.
AU: Sculley-DG; Dawson-PA; Emmerson-BT; Gordon-RB
AD: Department of Medicine, Princess Alexandra Hospital, University of Queensland, Australia.
SO: Hum-Genet. 1992 Nov; 90(3): 195-207
ISSN: 0340-6717
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: Hypoxanthine-guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8) is a purine salvage enzyme that catalyses the conversion of hypoxanthine and guanine to their respective mononucleotides. Partial deficiency of this enzyme can result in the overproduction of uric acid leading to a severe form of gout, whilst a virtual absence of HPRT activity causes the Lesch-Nyhan syndrome which is characterised by hyperuricaemia, mental retardation, choreoathetosis and compulsive self-mutilation. The HPRT-encoding gene is located on the X chromosome in the region q26-q27 and consists of nine exons and eight introns totalling 57 kb. This gene is transcribed to produce an mRNA of 1.6 kb, which contains a protein encoding region of 654 nucleotides. With the advent of increasingly refined techniques of molecular biology, it has been possible to study the HPRT gene of individuals with a deficiency in HPRT activity to determine the genetic basis of the enzyme deficiency. Many different mutations throughout the coding region have been described, but in the absence of precise information on the three-dimensional structure of the HPRT protein, it remains difficult to determine any consistent correlation between the structure and function of the enzyme.
MESH: Base-Sequence; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-diagnosis; Molecular-Sequence-Data; Mutation-
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-genetics
TG: Human
GS: HPRT
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 93138599
UD: 9304
MEDLINE EXPRESS (R) 1991-1995 66 of 122
TI: Molecular analysis of five independent Japanese mutant genes responsible for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency.
AU: Yamada-Y; Goto-H; Suzumori-K; Adachi-R; Ogasawara-N
AD: Department of Genetics, Aichi Prefectural Colony, Japan.
SO: Hum-Genet. 1992 Dec; 90(4): 379-84
ISSN: 0340-6717
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients. Using the polymerase chain reaction (PCR) technique coupled with direct sequencing, the nucleotide sequences of the entire HPRT coding region amplified from the cDNA and also of each exon amplified form the genomic DNA were analyzed. Three independent point mutations in the coding region were detected in the partially HPRT deficient patient (Case 1) and in two Lesch-Nyhan patients (Case 2 and 3), resulting in single amino acid substitutions. The family study of Case 3, utilizing a PvuII restriction site created in the mutant gene, indicated that the mother was a heterozygote, and a sister and a fetal brother had inherited the normal HPRT gene from the mother. In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene was deleted, and RNA splicing was missing in both mutants. A 4-bp deletion at the 5' end of exon 4 resulted in formation of three different types of abnormal mRNA (Case 4). The other mutant (Case 5) produced abnormal mRNA including 26 bp of intron 8 instead of the deleted 58 bp at the 5' end of exon 9, because of a 74-bp deletion from intron 8 to exon 9.
MESH: Amino-Acid-Sequence; Base-Sequence; DNA-; Electrophoresis,-Agar-Gel; Gout-enzymology; Gout-genetics; Hypoxanthine-Phosphoribosyltransferase-genetics; Japan-; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Pedigree-; Polymerase-Chain-Reaction; RNA-Splicing; Sequence-Deletion
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Point-Mutation
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 93131266
UD: 9304
SI: GENBANK/S53162; GENBANK/S52910; GENBANK/S52911; GENBANK/S52912; GENBANK/S52913; GENBANK/S52914; GENBANK/S78409; GENBANK/S78411; GENBANK/S78413; GENBANK/S78753
MEDLINE EXPRESS (R) 1991-1995 67 of 122
TI: Jacobus de Voragine (1230-1298): first to describe a Lesch-Nyhan syndrome?
AU: Beck-CT
AD: Kreiskrankenhaus Burg, Magdeburg, Germany.
SO: Eur-J-Pediatr-Surg. 1992 Dec; 2(6): 355-6
ISSN: 0930-7248
PY: 1992
LA: ENGLISH
CP: GERMANY
MESH: History-of-Medicine,-Medieval
MESH: *Lesch-Nyhan-Syndrome-history
TG: Human; Male
PT: HISTORICAL-ARTICLE; HISTORICAL-BIOGRAPHY; JOURNAL-ARTICLE
PS: de-Voragine-J
AN: 93120038
UD: 9304
MEDLINE EXPRESS (R) 1991-1995 68 of 122
TI: Lesch-Nyhan syndrome in a girl.
AU: van-Bogaert-P; Ceballos-I; Desguerre-I; Telvi-L; Kamoun-P; Ponsot-G
AD: Department of Paediatric Neurology, Hopital Saint-Vincent-De-Paul, Paris, France.
SO: J-Inherit-Metab-Dis. 1992; 15(5): 790-1
ISSN: 0141-8955
PY: 1992
LA: ENGLISH
CP: NETHERLANDS
MESH: Blotting,-Southern; Child-; DNA-analysis; Heterozygote-; Lesch-Nyhan-Syndrome-diagnosis
MESH: *Lesch-Nyhan-Syndrome-genetics
TG: Case-Report; Female; Human
PT: JOURNAL-ARTICLE
RN: 9007-49-2
NM: DNA
AN: 93060878
UD: 9302
MEDLINE EXPRESS (R) 1991-1995 69 of 122
TI: Functional analysis of brain dopamine systems in a genetic mouse model of Lesch-Nyhan syndrome.
AU: Jinnah-HA; Langlais-PJ; Friedmann-T
AD: Department of Neurosciences, University of California San Diego School of Medicine, La Jolla.
SO: J-Pharmacol-Exp-Ther. 1992 Nov; 263(2): 596-607
ISSN: 0022-3565
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: The Lesch-Nyhan syndrome is a neurogenetic disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The disorder is characterized by prominent neurobehavioral abnormalities which appear to result in part from dysfunction of striatal dopamine systems. HPRT-deficient (HPRT-) mutant strains of mice have been produced as animal models for this syndrome, but these animals exhibit none of the neurobehavioral abnormalities seen in Lesch-Nyhan patients. The present studies describe the behavioral responses of three strains of mice carrying one of two mutations in the HPRT gene to agents which interact with brain dopamine systems. HPRT- mice are more sensitive than age- and sex-matched littermates to the motor-activating properties of dopamine-releasing agents (amphetamine, amfonelic acid and methylphenidate), but not dopamine uptake inhibitors (GBR 12909 and nomifensine). The enhanced sensitivity of the HPRT- mice to the dopamine-releasing agents is not caused by dopamine receptor supersensitivity, because the HPRT- mice do not show enhanced motor responses to the direct D1/D2 dopamine receptor agonist apomorphine or to the selective D1 dopamine receptor agonist SKF 38393. The function of regulatory dopamine autoreceptors, as assessed by suppression of spontaneous motor activity by low doses of R(-)-propylnorapomorphine, also appears normal in the HPRT- mice. Biochemical analysis shows that the HPRT- mice have significantly lower levels of dopamine (-45%), but normal levels of tyrosine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine in the caudoputamen. In contrast to the deficit in caudoputamen dopamine, no deficits were noted in the accumbens of the HPRT- mice. These results indicate the existence of an inherent abnormality in the dopamine systems in the brains of HPRT- mice, despite their apparently normal spontaneous behavior.
MESH: Amphetamines-analysis; Amphetamines-pharmacology; Amphetamines-pharmacokinetics; Apomorphine-pharmacology; Disease-Models,-Animal; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-metabolism; Methylphenidate-pharmacology; Mice-; Mice,-Inbred-C57BL; Motor-Activity-drug-effects; Naphthyridines-pharmacology; SKandF-38393-pharmacology
MESH: *Brain-Chemistry; *Dopamine-metabolism; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Animal; Female; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD20034HDNICHD; S10RR0475401RRNCRR
RN: EC 2.4.2.8; 0; 0; 113-45-1; 15180-02-6; 51-61-6; 58-00-4; 67287-49-4
NM: Hypoxanthine-Phosphoribosyltransferase; Amphetamines; Naphthyridines; Methylphenidate; amfonelic-acid; Dopamine; Apomorphine; SK&F-38393
AN: 93058556
UD: 9302
MEDLINE EXPRESS (R) 1991-1995 70 of 122
TI: Renal ultrasonographic appearances at presentation in an infant with Lesch-Nyhan syndrome.
AU: Ludman-CN; Dicks-Mireaux-C; Saunders-AJ
AD: Department of Radiology, Guy's Hospital, London, UK.
SO: Br-J-Radiol. 1992 Aug; 65(776): 724-5
ISSN: 0007-1285
PY: 1992
LA: ENGLISH
CP: ENGLAND
MESH: Infant,-Newborn
MESH: *Kidney-ultrasonography; *Lesch-Nyhan-Syndrome-ultrasonography
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 93006891
UD: 9301
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 71 of 122
TI: Self-inflicted ocular mutilation in the pediatric age group.
AU: Ashkenazi-I; Shahar-E; Brand-N; Bartov-E; Blumenthal-M
AD: Goldschleger Eye Institute, Tel-Hashomer, Israel.
SO: Acta-Paediatr. 1992 Aug; 81(8): 649-51
ISSN: 0803-5253
PY: 1992
LA: ENGLISH
CP: NORWAY
AB: Three mentally retarded children with severe self-inflicted ocular injuries are presented. All three suffered from severe ocular injuries including retinal detachment resulting in progressive visual loss and even blindness. Self-inflicted injuries to the eyes, including self enucleation, is an extremely uncommon form of behavior, rarely encountered by pediatricians. The risk of ocular morbidity is high if the diagnosis is overlooked. Technical advances in ophthalmology permit much improvement in some formerly hopeless cases of ocular self-mutilation, but there is still no accurate method to repair destroyed retinal or nervous tissue. Early identification of patients at risk of ocular self-mutilation is essential in order to prevent or minimize such severe ocular injuries.
MESH: Child-
MESH: *Eye-Injuries-etiology; *Lesch-Nyhan-Syndrome-complications; *Mental-Retardation-complications; *Self-Mutilation-etiology
TG: Case-Report; Female; Human; Male
PT: JOURNAL-ARTICLE
AN: 93005362
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 72 of 122
TI: Mouse models of hypoxanthine phosphoribosyltransferase deficiency.
AU: Williamson-DJ; Hooper-ML; Melton-DW
AD: Department of Pathology, University Medical School, Edinburgh, UK.
SO: J-Inherit-Metab-Dis. 1992; 15(4): 665-73
ISSN: 0141-8955
PY: 1992
LA: ENGLISH
CP: NETHERLANDS
AB: Lesch--Nyhan syndrome is an X-linked disease caused by the deficiency of hypoxanthine phosphoribosyltransferase, an enzyme involved in the purine salvage pathways. It is characterized by severe gout, choreoathetosis, self-mutilatory behaviour and mental retardation. The derivation of mice genetically deficient in this enzyme may help to elucidate the pathogenesis of the neurological abnormality where previously models using drug administration to mimic the disorder have had to suffice.
MESH: Behavior,-Animal; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Mice-; Mice,-Transgenic; X-Chromosome
MESH: *Disease-Models,-Animal; *Hypoxanthine-Phosphoribosyltransferase-deficiency
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 92408236
UD: 9212
MEDLINE EXPRESS (R) 1991-1995 73 of 122
TI: [Retrospective diagnosis of Lesch-Nyhan syndrome]
TO: Retrospektive Diagnose eines Lesch-Nyhan-Syndroms.
AU: Rose-I
AD: Abteilung fur Kinderpathologie, Medizinischen Akademie Magdeburg, Deutschland.
SO: Zentralbl-Pathol. 1992 Jun; 138(3): 240-3
ISSN: 0863-4106
PY: 1992
LA: GERMAN; NON-ENGLISH
CP: GERMANY
AB: Lesch-Nyhan syndrome was retrospectively diagnosed by postmortem examination and family history in a male infant who had lived to the age of six months. Pathologico-anatomic findings included strongly pronounced uric acid nephropathy with tophaceous deposits and urate calculi in the renal pelvis as well as pedatrophia and anaemia.
MESH: Child,-Preschool; English-Abstract; Kidney-pathology; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-pathology; Retrospective-Studies
MESH: *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 92399404
UD: 9212
MEDLINE EXPRESS (R) 1991-1995 74 of 122
TI: Extracorporeal shock wave lithotripsy and xanthine calculi in Lesch-Nyhan syndrome.
AU: Morino-M; Shiigai-N; Kusuyama-H; Okada-K
AD: Department of Pediatrics, Saitama Medical School, Japan.
SO: Pediatr-Radiol. 1992; 22(4): 304
ISSN: 0301-0449
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: We report a case of Lesch-Nyhan syndrome (LNS) with urinary xanthine calculi. At eight years of age calculi in the renal pelvis were successfully disintegrated by extracorporeal shock wave lithotripsy (ESWL) without any complications. Follow-up sonography is very useful for management of patients with LNS, particularly when they are on allopurinol therapy.
MESH: Allopurinol-therapeutic-use; Infant-; Kidney-Calculi-chemistry; Kidney-Calculi-therapy
MESH: *Allopurinol-adverse-effects; *Kidney-Calculi-chemically-induced; *Lesch-Nyhan-Syndrome-drug-therapy; *Lithotripsy-; *Xanthines-analysis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 315-30-0; 69-89-6
NM: Xanthines; Allopurinol; xanthine
AN: 92396473
UD: 9212
MEDLINE EXPRESS (R) 1991-1995 75 of 122
TI: Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications.
AU: Monnat-RJ Jr; Chiaverotti-TA; Hackmann-AF; Maresh-GA
AD: Department of Pathology SM-30, University of Washington, Seattle 98195.
SO: Genomics. 1992 Jul; 13(3): 788-96
ISSN: 0888-7543
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: We have determined the genetic stability of three independent intragenic human HPRT gene duplications and the structure of each duplication at the nucleotide sequence level. Two of the duplications were isolated as spontaneous mutations from the HL60 human myeloid leukemia cell line, while the third was originally identified in a Lesch-Nyhan patient. All three duplications are genetically unstable and have a reversion rate approximately 100-fold higher than the rate of duplication formation. The molecular structures of these duplications are similar, with direct duplication of HPRT exons 2 and 3 and of 6.8 kb (HL60 duplications) or 13.7 kb (Lesch-Nyhan duplication) of surrounding HPRT sequence. Nucleotide sequence analyses of duplication junctions revealed that the HL60-derived duplications were generated by unequal homologous recombination between clusters of Alu repeats contained in HPRT introns 1 and 3, while the Lesch-Nyhan duplication was generated by the nonhomologous insertion of duplicated HPRT DNA into HPRT intron 1. These results suggest that duplication substrates of different lengths can be generated from the human HPRT exon 2-3 region and can undergo either homologous or nonhomologous recombination with the HPRT locus to form gene duplications.
MESH: Base-Sequence; DNA-genetics; DNA-Mutational-Analysis; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Models,-Genetic; Molecular-Sequence-Data; RNA,-Messenger-genetics; Tumor-Cells,-Cultured-enzymology
MESH: *Genes,-Reiterated; *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Human; Support,-U.S.-Gov't,-P.H.S.
GS: HPRT
PT: JOURNAL-ARTICLE
CN: R29CA48022CANCI; P01AG01751AGNIA
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; RNA,-Messenger; DNA
AN: 92347878
UD: 9211
SI: GENBANK/M84541; GENBANK/M84542; GENBANK/M84543; GENBANK/M84544; GENBANK/M84534; GENBANK/M84535; GENBANK/M84536; GENBANK/M84537; GENBANK/M84538; GENBANK/M84539
MEDLINE EXPRESS (R) 1991-1995 76 of 122
TI: [Prenatal diagnosis of Lesch-Nyhan syndrome]
TO: Diagnostico prenatal del sindrome de Lesch-Nyhan.
AU: Mateos-Anton-F; Garcia-Puig-J
AD: Servicio de Bioquimica Clinica, Hospital La Paz, Universidad Autonoma, Madrid.
SO: Neurologia. 1992 Apr; 7(4): 63-9
ISSN: 0213-4853
PY: 1992
LA: SPANISH; NON-ENGLISH
CP: SPAIN
MESH: Pregnancy-
MESH: *Fetal-Diseases-diagnosis; *Lesch-Nyhan-Syndrome-diagnosis; *Prenatal-Diagnosis
TG: Female; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 92329145
UD: 9210
MEDLINE EXPRESS (R) 1991-1995 77 of 122
TI: Cognitive abilities of patients with Lesch-Nyhan disease.
AU: Anderson-LT; Ernst-M; Davis-SV
AD: New York University School of Medicine.
SO: J-Autism-Dev-Disord. 1992 Jun; 22(2): 189-203
ISSN: 0162-3257
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Parents of 42 patients with Lesch-Nyhan disease completed a questionnaire systematizing caregiver observations of the subject's behavior during a wide variety of daily events. Responses were grouped in nine categories reflecting different aspects of cognitive skills. Only 1 boy appears to have any significant generalized cognitive impairment. The patients' memory for both recent and past events is excellent, their emotional life has a normal range of reactions and is appropriate; they have good concentration, are capable of abstract reasoning, have good self-awareness, and are highly social. However, they are behind in academic ability, with only 15% at grade level for math and reading. Implications for designing educational activities, parenting or caregiver strategies, and research methodology are discussed.
MESH: Adolescence-; Adult-; Awareness-; Behavior-Therapy; Child-; Child,-Preschool; Combined-Modality-Therapy; Language-Development-Disorders-diagnosis; Language-Development-Disorders-psychology; Language-Development-Disorders-therapy; Lesch-Nyhan-Syndrome-psychology; Lesch-Nyhan-Syndrome-therapy; Mental-Retardation-diagnosis; Mental-Retardation-psychology; Mental-Retardation-therapy; Self-Injurious-Behavior-diagnosis; Self-Injurious-Behavior-psychology; Self-Injurious-Behavior-therapy; Social-Adjustment; Social-Behavior; Social-Environment; Thinking-
MESH: *Achievement-; *Intelligence-; *Lesch-Nyhan-Syndrome-diagnosis; *Neuropsychological-Tests
TG: Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 1T32MH18915MHNIMH
AN: 92324989
UD: 9210
MEDLINE EXPRESS (R) 1991-1995 78 of 122
TI: Mutation analysis and prenatal diagnosis in a Lesch-Nyhan family showing non-random X-inactivation interfering with carrier detection tests.
AU: Marcus-S; Steen-AM; Andersson-B; Lambert-B; Kristoffersson-U; Francke-U
AD: Department of Clinical Genetics, Karolinska Institute, Stockholm, Sweden.
SO: Hum-Genet. 1992 Jun; 89(4): 395-400
ISSN: 0340-6717
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: A nonsense mutation at the CpG-site in the codon for Arg(169) in the gene for hypoxanthine phosphoribosyltransferase (hprt) was identified by genomic polymerase chain reaction (PCR) and DNA sequencing in cultured fibroblasts from two brothers with Lesch Nyhan's syndrome. The recurrence of mutation at this CpG-site in several unrelated Lesch-Nyhan families suggests that deamination of 5-methylcytosine is a possible mechanism for mutagenesis. The level of hprt-mRNA in the fibroblasts of the patients was similar to that in healthy controls, whereas hprt-enzyme activity was not detectable. The mutation in this family was also identified in five female relatives and prenatally in a male fetus. Unexpectedly, results from hair follicle analyses and fibroblast selection studies in 8-azaguanine and 6-thioguanine medium showed a non-carrier phenotype in three of the female heterozygotes, whereas X-inactivation mosaicism was demonstrated in one heterozygote. A possible explanation for the apparent non-random X-inactivation in this family is the co-existence of the hprt mutation with an undefined X-linked lethal mutation. This observation is of practical relevance for carrier detection in other Lesch-Nyhan families.
MESH: Base-Sequence; Cells,-Cultured; Fetal-Diseases-diagnosis; Fetal-Diseases-genetics; Heterozygote-; Hypoxanthine-Phosphoribosyltransferase-metabolism; Lesch-Nyhan-Syndrome-diagnosis; Molecular-Sequence-Data; Mosaicism-genetics; Mutation-genetics; Pedigree-; Polymerase-Chain-Reaction; Repetitive-Sequences,-Nucleic-Acid-genetics
MESH: *Dosage-Compensation-Genetics; *Heterozygote-Detection; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Prenatal-Diagnosis
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
GS: hprt
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 92316508
UD: 9210
MEDLINE EXPRESS (R) 1991-1995 79 of 122
TI: A female patient with Lesch-Nyhan syndrome.
AU: Yukawa-T; Akazawa-H; Miyake-Y; Takahashi-Y; Nagao-H; Takeda-E
AD: Ehime Disabled Children's Hospital, Japan.
SO: Dev-Med-Child-Neurol. 1992 Jun; 34(6): 543-6
ISSN: 0012-1622
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: The authors report the second case of a female with typical Lesch-Nyhan syndrome. She exhibited athetoid movement, self-multilation, mental retardation and spasticity. Laboratory investigations revealed hyperuricaemia, hyperuricosuria and decreased erythrocyte hypoxanthine guanine phosphoribosyl transferase activity. She has normal female external genitalia and karyotype. Her parents are non-consanguineous and there is no family member with gout, nephropathy or any psychoneurological disorder. To prevent self-stimulation, it was necessary to fix the patient's upper extremities to the backrest of her wheelchair. The authors also describe an apparatus that limits elbow flexion.
MESH: Child-; Karyotyping-; Lesch-Nyhan-Syndrome-epidemiology; Lesch-Nyhan-Syndrome-genetics; Pedigree-; Self-Mutilation-prevention-and-control; Sex-Factors
MESH: *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Female; Human
PT: JOURNAL-ARTICLE
AN: 92307163
UD: 9210
MEDLINE EXPRESS (R) 1991-1995 80 of 122
TI: Animal models point the way to human clinical trials [news]
AU: Kolberg-R
SO: Science. 1992 May 8; 256(5058): 772-3
ISSN: 0036-8075
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
MESH: Clinical-Trials; Disease-Models,-Animal; Hereditary-Diseases-genetics; Hypoxanthine-Phosphoribosyltransferase-deficiency; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-therapy; Research-methods
MESH: *Gene-Therapy; *Hereditary-Diseases-therapy
TG: Animal; Human
PT: NEWS
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 92271192
UD: 9208
MEDLINE EXPRESS (R) 1991-1995 81 of 122
TI: The Lesch-Nyhan syndrome--an under-recognised condition in South Africa? A case report.
AU: Gilbert-RD; Wiggelinkhuizen-J; Harley-EH; Marinaki-A
AD: Department of Paediatrics, University of Cape Town.
SO: S-Afr-Med-J. 1992 Apr 4; 81(7): 375-7
ISSN: 0038-2469
PY: 1992
LA: ENGLISH
CP: SOUTH-AFRICA
AB: The Lesch-Nyhan syndrome is a rare inborn error of purine metabolism caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which results in mental retardation with characteristic self-mutilation, spasticity, extrapyramidal signs and hyperuricaemia. The clinical and biochemical findings in an 18-month-old boy, who presented with renal calculi and was shown to have less than 1% of normal HGPRT activity, are reported. The obvious neurological abnormalities had previously been thought to be due to hypoxic-ischaemic encephalopathy. The expected incidence of this disease is much higher than the known number of cases diagnosed.
MESH: Athetosis-genetics; Infant,-Newborn; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Self-Mutilation; South-Africa
MESH: *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 92221301
UD: 9207
MEDLINE EXPRESS (R) 1991-1995 82 of 122
TI: [Screening for enzyme abnormality causing hyperuricemia]
AU: Higashino-K; Yamamoto-T; Moriwaki-Y
AD: Third Department of Internal Medicine, Hyogo College of Medicine.
SO: Nippon-Rinsho. 1991 May; 49(5): 1009-15
ISSN: 0047-1852
PY: 1991
LA: JAPANESE; NON-ENGLISH
CP: JAPAN
MESH: Glycogen-Storage-Disease-Type-I-diagnosis; Lesch-Nyhan-Syndrome-diagnosis
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Ribose-Phosphate-Pyrophosphokinase-metabolism; *Uric-Acid-blood
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8; EC 2.7.6.1; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Ribose-Phosphate-Pyrophosphokinase; Uric-Acid
AN: 91295304
UD: 9110
MEDLINE EXPRESS (R) 1991-1995 83 of 122
TI: Orotidine accumulation in human erythrocytes during allopurinol therapy: association with high urinary oxypurinol-7-riboside concentrations in renal failure and in the Lesch-Nyhan syndrome.
AU: Simmonds-HA; Reiter-S; Davies-PM; Cameron-JS
AD: Purine Research Laboratory, Clinical Science Laboratories, UMDS, Guy's Hospital Medical School, London.
SO: Clin-Sci-Colch. 1991 Mar; 80(3): 191-7
ISSN: 0143-5221
PY: 1991
LA: ENGLISH
CP: ENGLAND
AB: 1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol. 2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome. 3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol. 4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations. 5. Increased erythrocyte levels of the pyrimidine-sugar UDP-glucose were also found in patients with the highest orotidine levels. 6. The combined results suggest a derangement of pyrimidine nucleotide metabolism during allopurinol therapy. We propose that erythrocyte orotidine formation results primarily from inhibition of orotidine-5'-monophosphate decarboxylase by oxypurinol-7-ribotide.
MESH: Allopurinol-therapeutic-use; Nucleotides-blood; Oxypurinol-blood; Oxypurinol-urine; Ribonucleosides-blood; Uridine-blood
MESH: *Allopurinol-metabolism; *Erythrocytes-metabolism; *Kidney-Failure,-Chronic-metabolism; *Lesch-Nyhan-Syndrome-metabolism; *Oxypurinol-analogs-and-derivatives; *Ribonucleosides-urine; *Uridine-analogs-and-derivatives
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 16220-08-9; 2465-59-0; 314-50-1; 315-30-0; 58-96-8
NM: Nucleotides; Ribonucleosides; oxypurinol-7-riboside; Oxypurinol; orotidine; Allopurinol; Uridine
AN: 91215890
UD: 9108
MEDLINE EXPRESS (R) 1991-1995 84 of 122
TI: The molecular characterisation of HPRT CHERMSIDE and HPRT COORPAROO: two Lesch-Nyhan patients with reduced amounts of mRNA.
AU: Gordon-RB; Dawson-PA; Sculley-DG; Emmerson-BT; Caskey-CT; Gibbs-RA
AD: Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
SO: Gene. 1991 Dec 15; 108(2): 299-304
ISSN: 0378-1119
PY: 1991
LA: ENGLISH
CP: NETHERLANDS
AB: A complete deficiency of the purine salvage enzyme, hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), in man results in the Lesch-Nyhan (LN) syndrome. Two unrelated patients with the full LN syndrome showed no evidence of a major alteration to the gene encoding HPRT (HPRT) by restriction endonuclease analysis, but exhibited negligible levels of HPRT mRNA on Northern blots. DNA from these patients was characterised further. Amplification, by the polymerase chain reaction (PCR), of individual HPRT-exon fragments from genomic DNA followed by nucleotide (nt) sequence analysis using automated technology, revealed single-base mutations in each patient. One patient has an insertion of a T within exon-2, which places a stop codon in frame, presumably resulting in premature termination of translation of the HPRT mRNA. The other patient has a G----A base substitution at the 5' end of intron-6, at the junction of exon-6 and intron-6. Although dot blot analysis indicated negligible HPRT mRNA in lymphoblast cells from both patients, we were successful in amplifying HPRT cDNA using PCR. Direct nt sequence analysis of the amplified cDNA confirmed the insertion of a T in exon-2 in the one patient and revealed a complete deletion of exon-6 in the other patient, the latter event presumably arising due to aberrant splicing of primary message. Both mutations were also confirmed by hybridisation of amplified genomic DNA with allele-specific oligodeoxyribonucleotide probes. This study illustrates two approaches for analysing DNA mutations at the molecular level and demonstrates the power of PCR technology in the study of genetic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Base-Sequence; Blotting,-Northern; Codon-genetics; Exons-genetics; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Mutation-genetics; Polymerase-Chain-Reaction; Translation,-Genetic-genetics
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Female; Human; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; Codon
AN: 92084152
UD: 9203
SI: GENBANK/S70058; GENBANK/S70064; GENBANK/D01026; GENBANK/D01027; GENBANK/S75343; GENBANK/S75344; GENBANK/S75345; GENBANK/S75347; GENBANK/S75348; GENBANK/S75349
MEDLINE EXPRESS (R) 1991-1995 85 of 122
TI: Identification of two independent Japanese mutant HPRT genes using the PCR technique.
AU: Yamada-Y; Goto-H; Ogasawara-N
AD: Department of Genetics, Institute for Developmental Research, Aichi, Japan.
SO: Adv-Exp-Med-Biol. 1991; 309B: 121-4
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Amino-Acid-Sequence; Base-Sequence; Chromosome-Deletion; DNA-genetics; DNA-Probes; Hypoxanthine-Phosphoribosyltransferase-deficiency; Japan-; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Mutation-; Polymerase-Chain-Reaction; RNA-Splicing
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Human; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA-Probes; DNA
AN: 92142870
UD: 9205
SI: GENBANK/S79313; GENBANK/S79315; GENBANK/S79316; GENBANK/S79318; GENBANK/S79320
MEDLINE EXPRESS (R) 1991-1995 86 of 122
TI: [Advances in the research on gene therapy]
AU: Zhang-LX; Han-JS
SO: Sheng-Li-Ko-Hsueh-Chin-Chan. 1991 Oct; 22(4): 304-7
ISSN: 0559-7765
PY: 1991
LA: CHINESE; NON-ENGLISH
CP: CHINA
MESH: Gene-Therapy-trends; Lesch-Nyhan-Syndrome-therapy; Neoplasms-therapy; Parkinson-Disease-therapy
MESH: *Gene-Therapy
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 92179667
UD: 9206
MEDLINE EXPRESS (R) 1991-1995 87 of 122
TI: Prenatal diagnosis of Lesch-Nyhan syndrome by purine analysis of amniotic fluid and cordocentesis.
AU: Mateos-FA; Puig-JG; Ramos-TH; Jimenez-ML; Romera-NM; Gonzalez-AG
AD: Division of Internal Medicine, La Paz Hospital, Universidad Autonoma, Madrid, Spain.
SO: Adv-Exp-Med-Biol. 1991; 309B: 47-50
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Adult-; Amniotic-Fluid-chemistry; Fetal-Blood-chemistry; Hypoxanthine-Phosphoribosyltransferase-deficiency; Hypoxanthines-analysis; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-metabolism; Pedigree-; Pregnancy-; Prenatal-Diagnosis; Uric-Acid-analysis; Xanthines-analysis
MESH: *Lesch-Nyhan-Syndrome-diagnosis; *Purines-analysis
TG: Case-Report; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0; 0; 68-94-0; 69-89-6; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Hypoxanthines; Purines; Xanthines; hypoxanthine; xanthine; Uric-Acid
AN: 92142938
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 88 of 122
TI: Analysis of forebrain dopaminergic pathways in HPRT-mice.
AU: Williamson-DJ; Sharkey-J; Clarke-AR; Jamieson-A; Arbuthnott-GW; Kelly-P; Melton-DW; Hooper-ML
AD: Department of Pathology, University of Edinburgh.
SO: Adv-Exp-Med-Biol. 1991; 309B: 269-72
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Behavior-physiology; Disease-Models,-Animal; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-metabolism; Lesch-Nyhan-Syndrome-psychology; Mice-; Mice,-Inbred-Strains; Mice,-Mutant-Strains; Receptors,-Dopamine-metabolism
MESH: *Dopamine-metabolism; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Prosencephalon-metabolism
TG: Animal; Male; Support,-Non-U.S.-Gov't
GS: hprt<up>b-m3<up>
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 51-61-6
NM: Hypoxanthine-Phosphoribosyltransferase; Receptors,-Dopamine; Dopamine
AN: 92142905
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 89 of 122
TI: Urinary pterins in Lesch-Nyhan syndrome.
AU: Sebesta-I; Krijt-J; Kmoch-S; Hyanek-J
AD: Department of Clinical Biochemistry, 1st Medical Faculty, Charles University, Prague, Czechoslovakia.
SO: Adv-Exp-Med-Biol. 1991; 309B: 261-4
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Biopterin-analogs-and-derivatives; Biopterin-urine; Central-Nervous-System-metabolism; Child,-Preschool; Guanosine-Triphosphate-metabolism; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-etiology
MESH: *Lesch-Nyhan-Syndrome-urine; *Pterins-urine
TG: Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 22150-76-1; 670-65-5; 86-01-1
NM: Hypoxanthine-Phosphoribosyltransferase; Pterins; Biopterin; neopterin; Guanosine-Triphosphate
AN: 92142903
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 90 of 122
TI: HPRT gene mutations in a female Lesch-Nyhan patient.
AU: Ogasawara-N; Yamada-Y; Goto-H
AD: Department of Genetics, Institute for Developmental Research, Aichi, Japan.
SO: Adv-Exp-Med-Biol. 1991; 309B: 109-12
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Adolescence-; Base-Sequence; Chromosome-Deletion; Dosage-Compensation-Genetics; DNA-chemistry; DNA-genetics; Hypoxanthine-Phosphoribosyltransferase-deficiency; Lesch-Nyhan-Syndrome-enzymology; Methylation-; Molecular-Sequence-Data; X-Chromosome
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Case-Report; Female; Human; Support,-Non-U.S.-Gov't
GS: HPRT
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 92142866
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 91 of 122
TI: Molecular analysis of hypoxanthine-guanine phosphoribosyltransferase deficiency in Japanese patients.
AU: Fujimori-S; Tagaya-T; Yamaoka-N; Kamatani-N; Akaoka-I
AD: Second Department of Internal Medicine, University of Teikyo, Tokyo, Japan.
SO: Adv-Exp-Med-Biol. 1991; 309B: 101-4
ISSN: 0065-2598
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Base-Sequence; DNA-genetics; DNA-Mutational-Analysis; Japan-; Lesch-Nyhan-Syndrome-enzymology; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Polymerase-Chain-Reaction
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 92142864
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 92 of 122
TI: Amphetamine-induced behavioral phenotype in a hypoxanthine-guanine phosphoribosyltransferase-deficient mouse model of Lesch-Nyhan syndrome.
AU: Jinnah-HA; Gage-FH; Friedmann-T
AD: Department of Neurosciences, School of Medicine, University of California, San Diego 92093-0634.
SO: Behav-Neurosci. 1991 Dec; 105(6): 1004-12
ISSN: 0735-7044
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: In humans, congenital deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a disorder known as the Lesch-Nyhan syndrome. Patients with this disorder exhibit a prominent neurobehavioral phenotype that results in part from dysfunction of catecholaminergic systems in the striatum. HPRT-deficient mice produced as animal models for this syndrome curiously exhibit no spontaneous neurobehavioral abnormalities. However, the present study demonstrates that HPRT-deficient mice are more sensitive than their HPRT-normal littermates to the ability of amphetamine to stimulate locomotor or stereotypic behaviors. This behavioral supersensitivity to amphetamine indicates the existence of an underlying subclinical abnormality of catecholaminergic systems in the brains of HPRT-deficient mice, analogous to findings in human Lesch-Nyhan patients.
MESH: Brain-physiopathology; Catecholamines-physiology; Chromosome-Deletion; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-physiopathology; Mice-; Mice,-Neurologic-Mutants; Motor-Activity-drug-effects; Motor-Activity-physiology; Stereotyped-Behavior-drug-effects; Stereotyped-Behavior-physiology
MESH: *Dextroamphetamine-pharmacology; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-chemically-induced; *Lesch-Nyhan-Syndrome-genetics; *Phenotype-
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HD20034HDNICHD
RN: EC 2.4.2.8; 0; 51-64-9
NM: Hypoxanthine-Phosphoribosyltransferase; Catecholamines; Dextroamphetamine
AN: 92134570
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 93 of 122
TI: Clinical quiz. Lesch-Nyhan syndrome.
AU: Bhagat-MM; Reid-CJ
AD: Department of Paediatrics, Guy's Hospital, London, UK.
SO: Pediatr-Nephrol. 1991 Nov; 5(6): 758-60
ISSN: 0931-041X
PY: 1991
LA: ENGLISH
CP: GERMANY
MESH: Creatinine-blood; Creatinine-urine; Hypoxanthine-Phosphoribosyltransferase-metabolism; Infant,-Newborn; Lesch-Nyhan-Syndrome-enzymology; Uric-Acid-blood; Uric-Acid-urine
MESH: *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 60-27-5; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Creatinine; Uric-Acid
AN: 92118631
UD: 9204
MEDLINE EXPRESS (R) 1991-1995 94 of 122
TI: Recurrent coma and Lesch-Nyhan syndrome.
AU: Lynch-BJ; Noetzel-MJ
AD: Department of Pediatrics, Washington University, St. Louis, Missouri.
SO: Pediatr-Neurol. 1991 Sep-Oct; 7(5): 389-91
ISSN: 0887-8994
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: A patient with Lesch-Nyhan syndrome has had 3 recurrent episodes of coma, each associated with an acute illness. Extensive investigation for known causes of coma has failed to yield a diagnosis. Although coma is not generally recognized as a feature of Lesch-Nyhan syndrome, similar patients have been reported previously. This and other episodic phenomena observed in Lesch-Nyhan syndrome may be explained by the disruption of cellular energy metabolism due to purine depletion, consequent to lack of the purine salvage pathway normally provided by the hypoxanthine-guanine-phosphoribosyl-transferase enzyme.
MESH: Coma-psychology; Infant-; Nephrocalcinosis-complications; Pneumonia-complications; Recurrence-
MESH: *Coma-etiology; *Lesch-Nyhan-Syndrome-complications
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 92109829
UD: 9204
MEDLINE EXPRESS (R) 1991-1995 95 of 122
TI: Comments on self-injurious behaviour [letter; comment]
CM: Comment on: Am J Psychiatry 1991 Mar;148(3):306-17
AU: King-BH; Poland-RE
SO: Am-J-Psychiatry. 1991 Nov; 148(11): 1617-8
ISSN: 0002-953X
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
MESH: Compulsive-Behavior-psychology; Institutionalization-; Lesch-Nyhan-Syndrome-complications; Lesch-Nyhan-Syndrome-psychology; Mental-Retardation-psychology; Self-Mutilation-psychology
MESH: *Mental-Retardation-complications; *Self-Mutilation-etiology
TG: Human
PT: COMMENT; LETTER
AN: 92026625
UD: 9201
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 96 of 122
TI: Bone marrow transplantation in Lesch-Nyhan disease.
AU: Endres-W; Helmig-M; Shin-YS; Albert-E; Wank-R; Ibel-H; Weiss-M; Hadorn-HB; Hass-R
AD: Universitats-Kinderklinik, Munchen, Germany.
SO: J-Inherit-Metab-Dis. 1991; 14(2): 270-1
ISSN: 0141-8955
PY: 1991
LA: ENGLISH
CP: NETHERLANDS
MESH: Adult-; Erythrocytes-enzymology; Hypoxanthine-Phosphoribosyltransferase-blood; Infant-
MESH: *Bone-Marrow-Transplantation; *Lesch-Nyhan-Syndrome-surgery
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 91359706
UD: 9112
MEDLINE EXPRESS (R) 1991-1995 97 of 122
TI: The pathogenesis of the Lesch-Nyhan syndrome: ATP use is positively related to hypoxanthine supply to hypoxanthine guanine phosphoribosyltransferase.
AU: Harkness-RA; McCreanor-GM; Greenwood-R
AD: Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Middlesex, UK.
SO: J-Inherit-Metab-Dis. 1991; 14(2): 202-14
ISSN: 0141-8955
PY: 1991
LA: ENGLISH
CP: NETHERLANDS
AB: In order to explain features of severe hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, the Lesch-Nyhan syndrome, a continuous supply of substrate, hypoxanthine, for the enzyme must be generated. This supply must be increased in association with increased ATP turnover. We have shown that ATP turnover continuously supplies hypoxanthine for recycling by the enzyme HPRT and that this supply increases curvilinearly with increasing ATP turnover. The effects of increasing exercise on ATP turnover were examined using a Latin square experimental design. The outputs of hypoxanthine, xanthine, urate and creatinine were measured. The data were then examined statistically.
MESH: Adult-; Aging-urine; Body-Mass-Index; Creatinine-urine; Exercise-physiology; Hypoxanthine-Phosphoribosyltransferase-metabolism; Hypoxanthines-urine; Kinetics-; Middle-Age; Uric-Acid-urine; Xanthines-urine
MESH: *Adenosine-Triphosphate-metabolism; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthines-metabolism; *Lesch-Nyhan-Syndrome-enzymology
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 0; 56-65-5; 60-27-5; 68-94-0; 69-89-6; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Hypoxanthines; Xanthines; Adenosine-Triphosphate; Creatinine; hypoxanthine; xanthine; Uric-Acid
AN: 91359694
UD: 9112
MEDLINE EXPRESS (R) 1991-1995 98 of 122
TI: Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects.
AU: Tarle-SA; Davidson-BL; Wu-VC; Zidar-FJ; Seegmiller-JE; Kelley-WN; Palella-TD
AD: Department of Internal Medicine, Rackham Arthritis Research Unit, University of Michigan, Ann Arbor 48109.
SO: Genomics. 1991 Jun; 10(2): 499-501
ISSN: 0888-7543
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Hypoxanthine--guanine phosphoribosyltransferase (HPRT) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. Previous studies of mutant HPRT proteins analyzed at the molecular level have shown a significant heterogeneity. This investigation further verifies this heterogeneity and identifies insertions, deletions, and point mutations. The direct sequencing of the polymerase chain reaction-amplified product of reverse-transcribed HPRT mRNA enabled the rapid identification of the mutations found in 17 previously uncharacterized cell lines derived from patients with the Lesch-Nyhan syndrome.
MESH: Cell-Line; DNA-Mutational-Analysis; Polymerase-Chain-Reaction
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: R01DK19045DKNIDDK; P60AR20557ARNIAMS
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 91301712
UD: 9110
MEDLINE EXPRESS (R) 1991-1995 99 of 122
TI: [HPRT deficiency]
AU: Fujimori-S; Yamanouchi-T; Akaoka-I
AD: Second Department of Internal Medicine, Teikyo University School of Medicine.
SO: Nippon-Rinsho. 1991 May; 49(5): 1036-42
ISSN: 0047-1852
PY: 1991
LA: JAPANESE; NON-ENGLISH
CP: JAPAN
MESH: Base-Sequence; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Uric-Acid-blood
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8; 69-93-2
NM: Hypoxanthine-Phosphoribosyltransferase; Uric-Acid
AN: 91295308
UD: 9110
MEDLINE EXPRESS (R) 1991-1995 100 of 122
TI: Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.
AU: Davidson-BL; Tarle-SA; Van-Antwerp-M; Gibbs-DA; Watts-RW; Kelley-WN; Palella-TD
AD: Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
SO: Am-J-Hum-Genet. 1991 May; 48(5): 951-8
ISSN: 0002-9297
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency causes the Lesch-Nyhan syndrome, an X-linked, purine metabolism disorder manifested by hyperuricemia, hyperuricaciduria, and neurologic dysfunction. Partial HPRT deficiency causes hyperuricemia and gout. One requirement for understanding the molecular basis of HPRT deficiency is the determination of which amino acids in this salvage enzyme are necessary for structural or catalytic competence. In this study we have used the PCR coupled with direct sequencing to determine the nucleotide and subsequent amino acid changes in 22 subjects representing 17 unrelated kindreds from the United Kingdom. These mutations were confirmed by using either RNase mapping or Southern analyses. In addition, experiments were done to determine enzyme activity and electrophoretic mobility, and predictive paradigms were used to study the impact of these amino acid substitutions on secondary structure.
MESH: Chromosome-Deletion; Hypoxanthine-Phosphoribosyltransferase-metabolism; Lesch-Nyhan-Syndrome-enzymology; Mutagenesis,-Insertional
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-genetics
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW-OF-REPORTED-CASES
CN: R01DK19045DKNIDDK; AR20557ARNIAMS
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 91206408
UD: 9107
MEDLINE EXPRESS (R) 1991-1995 101 of 122
TI: Renal sonography in long standing Lesch-Nyhan syndrome.
AU: Kenney-IJ
AD: X-ray Department, Royal Alexandra Hospital for Sick Children, Brighton.
SO: Clin-Radiol. 1991 Jan; 43(1): 39-41
ISSN: 0009-9260
PY: 1991
LA: ENGLISH
CP: ENGLAND
AB: The Lesch-Nyhan syndrome is an x-linked defect of purine metabolism resulting in its classical form in major neurodevelopmental abnormality, hyperuricaemia, and hyperuricosuria. Uric acid calculi and crystalluria are common. Allopurinol is the main method of reducing serum and urinary uric acid levels, but results in xanthinuria and oxypurinoluria, both of which may cause crystal nephropathy and calculi. The variable ultrasonic appearances of multiple calculi and increased medullary echogenicity in four cases of long-standing treated disease and the nature of the renal disorder, which is at least partially iatrogenic, are described.
MESH: Adolescence-; Adult-; Allopurinol-adverse-effects; Child-; Kidney-Calculi-etiology; Lesch-Nyhan-Syndrome-complications; Time-Factors
MESH: *Kidney-Calculi-ultrasonography; *Lesch-Nyhan-Syndrome-drug-therapy
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
RN: 315-30-0
NM: Allopurinol
AN: 91152975
UD: 9106
MEDLINE EXPRESS (R) 1990 102 of 122
TI: Orthopaedic manifestations in congenitally insensate patients.
AU: Guidera-KJ; Multhopp-H; Ganey-T; Ogden-JA
AD: Shriners Hospital for Crippled Children, Tampa Unit, FL 33612-9499.
SO: J-Pediatr-Orthop. 1990 Jul-Aug; 10(4): 514-21
ISSN: 0271-6798
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: The spectrum of orthopaedic problems in eight congenitally insensate patients was reviewed. The conditions included congenital insensitivity to pain, Riley-Day syndrome, and Lesch-Nyhan syndrome. In each of these conditions, the patient has an abnormality of interpretation of painful stimuli or lacks normal pain avoidance, leading to self-inflicted damage. The orthopaedic problems and complications included fracture, self-mutilation, autoamputation, osteomyelitis, septic arthritis, Charcot joints, scoliosis, and dislocation. Effective management consists of early diagnosis and patient/parent education to prevent as many complications as possible. Fractures may be treated conservatively, while progressive scoliosis requires operative intervention. Osteomyelitis, septic arthritis, and Charcot joints require appropriate operative treatment.
MESH: Adolescence-; Adult-; Bone-Diseases-pathology; Bone-Diseases-radiography; Child-; Child,-Preschool; Dysautonomia,-Familial-physiopathology; Dysautonomia,-Familial-psychology; Infant-; Lesch-Nyhan-Syndrome-physiopathology; Lesch-Nyhan-Syndrome-psychology; Pain-Insensitivity,-Congenital-physiopathology; Pain-Insensitivity,-Congenital-psychology; Patient-Education
MESH: *Bone-Diseases-etiology; *Dysautonomia,-Familial-complications; *Lesch-Nyhan-Syndrome-complications; *Pain-Insensitivity,-Congenital-complications
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
AN: 90293137
UD: 9010
MEDLINE EXPRESS (R) 1990 103 of 122
TI: Levels of hypoxanthine phosphoribosyltransferase RNA in human cells.
AU: Steen-AM; Luthman-H; Hellgren-D; Lambert-B
AD: Department of Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
SO: Exp-Cell-Res. 1990 Feb; 186(2): 236-44
ISSN: 0014-4827
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: The gene for the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT) is expressed at a low level in many cells. As is the case with several other "housekeeping genes," thorough studies of hprt gene regulation have been hampered by the low levels of its mRNA. We have used RNA/RNA hybridization in solution to determine the concentration of hprt-RNA in human cells. The sensitivity and specificity of the method have been validated, and it is shown that hprt-RNA can be accurately determined at a level of a few mRNA molecules per cell. As expected for a housekeeping gene, low and relatively constant hprt-RNA levels (0.3-0.8 pg/micrograms DNA) were found in primary cultures of normal amnion cells and fibroblasts, EBV-transformed lymphoblastoid cell lines, neuroblastoma, glioblastoma, and melanoma cell cultures. While resting lymphocytes were found to contain very low amounts of hprt-RNA, lymphocytes stimulated with phytohemagglutinin (PHA) showed a 10-fold increase to about 0.8-1.2 pg/microgram DNA, which corresponds to 6-10 hprt-RNA molecules per cell. The level started to increase about 20 h after PHA stimulation, 5-10 h before the onset of DNA synthesis, and a steady-state level was reached after 2-3 days in culture. In PHA-stimulated lymphocytes from two brothers with inherited HPRT deficiency (Lesch-Nyhans syndrome), the hprt-RNA level in PHA-stimulated lymphocytes was only about 25% of that in normal subjects. In T-cells selected for HPRT deficiency by growth in 6-thioguanine medium, the levels of hprt-RNA were either normal or very low, which probably reflects the different nature of the mutations involved. These results demonstrate the sensitivity of this method for determinations of low levels of RNA and clearly show induction of hprt-RNA after mitogenic stimulation of human lymphocytes.
MESH: Amnion-enzymology; Cell-Line,-Transformed; Cells,-Cultured; Clone-Cells; Fibroblasts-enzymology; Glioma-enzymology; Lesch-Nyhan-Syndrome-enzymology; Lymphocytes-enzymology; Melanoma-enzymology; Mutation-; Neuroblastoma-enzymology; Nucleic-Acid-Hybridization; Phytohemagglutinins-pharmacology; RNA-metabolism; RNA-Probes; T-Lymphocytes-enzymology; Tumor-Cells,-Cultured
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *RNA-analysis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0; 63231-63-0
NM: Hypoxanthine-Phosphoribosyltransferase; RNA-Probes; RNA
AN: 90127098
UD: 9005
MEDLINE EXPRESS (R) 1990 104 of 122
TI: Evidence that lack of brain dopamine during development can increase the susceptibility for aggression and self-injurious behavior by influencing D1-dopamine receptor function.
AU: Breese-GR; Criswell-HE; Mueller-RA
AD: Brain and Development Research Center, University of North Carolina, School of Medicine, Chapel Hill.
SO: Prog-Neuropsychopharmacol-Biol-Psychiatry. 1990; 14 Suppl: S65-80
ISSN: 0278-5846
PY: 1990
LA: ENGLISH
CP: ENGLAND
AB: 1. Lesch-Nyhan disease has a defined neurological lesion that is accompanied by abnormal motor function, aggression and self-injurious behavior. 2. The dopamine deficiency in Lesch-Nyhan disease has been modelled by destroying dopamine-containing neurons in neonatal rats with 6-hydroxydopamine. 3. Because D1-dopamine antagonists will block self-injurious behavior induced by L-DOPA in neonatal-6-OHDA-lesioned rats, D1-dopamine antagonists are proposed as a potential therapy for aggression and self-injurious behavior in patients with these symptoms. 4. The determination that the drug SCH-12679, which exhibited effectiveness against aggressiveness in mentally retarded patients, is a D1-dopamine antagonist supports the view that new D1-dopamine antagonists being developed will be an effective therapy for some types of aberrant behavior in this population.
MESH: Anti-Anxiety-Agents-therapeutic-use; Child-; Dopamine-physiology; Lesch-Nyhan-Syndrome-psychology; Mental-Retardation-drug-therapy; Mental-Retardation-physiopathology; Mental-Retardation-psychology; Receptors,-Dopamine-antagonists-and-inhibitors; SKandF-38393-analogs-and-derivatives; SKandF-38393-pharmacology; SKandF-38393-therapeutic-use
MESH: *Aggression-; *Child-Development; *Dopamine-deficiency; *Lesch-Nyhan-Syndrome-physiopathology; *Receptors,-Dopamine-physiology; *Violence-
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: HD03110HDNICHD; HD23042HDNICHD; MH36294MHNIMH
RN: 0; 0; 0; 20012-08-2; 51-61-6; 67287-49-4
NM: Anti-Anxiety-Agents; Receptors,-Dopamine-D1; Receptors,-Dopamine; trimopam; Dopamine; SK&F-38393
AN: 91271606
UD: 9109
MEDLINE EXPRESS (R) 1990 105 of 122
TI: Quantitative histologic study of the sural nerve in Lesch-Nyhan syndrome.
AU: Origuchi-Y; Miyoshino-S; Mishima-K; Mine-K
AD: Department of Pediatrics, Nishibeppu National Hospital, Beppu, Japan.
SO: Pediatr-Neurol. 1990 Sep-Oct; 6(5): 353-5
ISSN: 0887-8994
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: The sural nerve of a 31-year-old man with Lesch-Nyhan syndrome obtained at autopsy was studied histologically. Large, myelinated nerve fibers were reduced in number and no myelinated nerve fibers larger than 5 microns were seen. Diameter distribution of myelinated nerve fibers did not demonstrate a bimodal pattern. The density of myelinated nerve fibers was 5,530/mm2 and was decreased as compared to the controls. On electron microscopic examination, lipid-like inclusions were observed in the cytoplasm of some Schwann cells. The role of these inclusions could not be elucidated, but reduction of larger myelinated nerve fibers suggests a peripheral nervous disorder in patients with this syndrome; therefore, patients with Lesch-Nyhan syndrome must be reappraised for disorders of the peripheral nervous system.
MESH: Adult-; Inclusion-Bodies-ultrastructure; Nerve-Fibers,-Myelinated-pathology; Nerve-Fibers,-Myelinated-ultrastructure; Schwann-Cells-ultrastructure; Sural-Nerve-ultrastructure
MESH: *Lesch-Nyhan-Syndrome-pathology; *Sural-Nerve-pathology
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 91054723
UD: 9103
MEDLINE EXPRESS (R) 1990 106 of 122
TI: Regulation of nicotinamide-adenine dinucleotide synthesis in erythrocytes of patients with hypoxanthine-guanine phosphoribosyltransferase deficiency and a patient with phosphoribosylpyrophosphate synthetase superactivity.
AU: Micheli-V; Simmonds-HA; Ricci-C
AD: Istituto di Chimica Biologica, Universita' di Siena, Italy.
SO: Clin-Sci-Colch. 1990 Feb; 78(2): 239-45
ISSN: 0143-5221
PY: 1990
LA: ENGLISH
CP: ENGLAND
AB: 1. The synthesis of nicotinamide-adenine dinucleotide from nicotinamide and nicotinic acid was compared over different time scales at both physiological (0.7 mumol/l) and high (0.2-3 mmol/l) substrate concentrations in erythrocytes from three patients with hypoxanthine-guanine phosphoribosyltransferase (hypoxanthine phosphoribosyltransferase, EC 2.4.2.8) deficiency (including one Lesch-Nyhan patient) and from one patient with phosphoribosylpyrophosphate synthetase superactivity. The above disorders are associated with grossly altered erythrocyte nicotinamide-adenine dinucleotide levels. 2. At the physiological substrate concentration and incubation times up to 2 h, nicotinamide proved the most efficient nicotinamide-adenine dinucleotide precursor for erythrocytes from both patients and control subjects. The conversion of nicotinamide to its mononucleotide, but not further metabolism, was impaired in phosphoribosylpyrophosphate synthetase-mutant cells. The Lesch-Nyhan and phosphoribosylpyrophosphate synthetase-mutant cells were unusual in that both showed no further stimulation of nucleotide synthesis at 18 mmol/l Pi compared with 1 mmol/l. 3. At the high substrate concentrations, using 18 mmol/l Pi, nicotinamide was a poor precursor in all instances. Using nicotinic acid, nucleotide formation was 30-fold that from nicotinamide, reaching its maximum at 0.2 mmol/l. Conversion of nicotinic acid to nicotinamide-adenine dinucleotide in the phosphoribosylpyrophosphate synthetase-mutant cells was again grossly impaired. 4. There was no evidence for increased nicotinamide-adenine dinucleotide breakdown in the phosphoribosylpyrophosphate synthetase-mutant cells under any of the above conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Adult-; Cells,-Cultured; Child-; Chromatography,-High-Pressure-Liquid; Lesch-Nyhan-Syndrome-metabolism; Niacinamide-metabolism; Nicotinic-Acids-metabolism
MESH: *Erythrocytes-metabolism; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Metabolism,-Inborn-Errors-metabolism; *NAD-biosynthesis; *Phosphotransferases-metabolism; *Ribose-Phosphate-Pyrophosphokinase-metabolism
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; EC 2.7; EC 2.7.6.1; 0; 53-84-9; 98-92-0
NM: Hypoxanthine-Phosphoribosyltransferase; Phosphotransferases; Ribose-Phosphate-Pyrophosphokinase; Nicotinic-Acids; NAD; Niacinamide
AN: 90183244
UD: 9006
MEDLINE EXPRESS (R) 1990 107 of 122
TI: Heterozygous expression of Lesch-Nyhan syndrome clinical and ultrastructural studies.
AU: Meguid-NA; Aboul-Ezz-EH; Seif-E; Temtamy-SA
AD: Human Genetics Department, National Research Center, Cairo, Egypt.
SO: J-Egypt-Public-Health-Assoc. 1990; 65(5-6): 585-600
ISSN: 0013-2446
PY: 1990
LA: ENGLISH
CP: EGYPT
AB: The study comprised two cases (male & female sibs) from one family, with Lesch-Nyhan Syndrome. They were subjected to clinical evaluation, pedigree construction, uric acid estimation in blood, urates in urine, metabolic screening of blood and urine for amino acids, examination of oral cavity, histological studies of the gingiva by light and electron microscopy as well as buccal smear for Barr & Y bodies (for the female). The proband, a six years old female presented with self-mutilation, mental retardation, hyperactivity and aggression. She had bitten her index finger causing amputation of its distal phalanx. On family study her younger brother (9 months) was found to have increased uric acid and less severe neurologic involvement. The serum uric acid level of the affected female was higher. Her Barr body showed normal pattern. Oral cavity examination showed no abnormalities. Histological examination of the gingiva showed macrophages around the blood vessels. Ultrastructural studies showed more or less normal epithelium. There was collection of macrophages around the blood vessels in the sub-epithelial layer, the cytoplasm of these macrophages contained stippled cytoplasmic inclusions. The surrounding connective tissue showed thin collagen fibers with sharp delineation between the epithelial and connective tissue layers indicating poor quality of collagen. There was no histological difference between the hemizygous male and the heterozygous female. The present study indicates heterozygous expression of Lesch-Nyhan Syndrome at both the clinical and the ultrastructural levels in favour of extreme lyonization or X-chromosome deletion in the affected female. Our findings also indicate that ultrastructural studies could be sensitive indicators of abnormal uric acid metabolism. Further studies are needed to compare the phenotypic expression of hemizygotes and heterozygotes with Lesch-Nyhan Syndrome at both the clinical and ultrastructural levels.
MESH: Child-; Gingiva-ultrastructure; Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-epidemiology; Pedigree-; Sensitivity-and-Specificity; Uric-Acid-blood; Uric-Acid-urine
MESH: *Heterozygote-Detection; *Lesch-Nyhan-Syndrome-genetics
TG: Case-Report; Female; Human; Male
PT: JOURNAL-ARTICLE
RN: 69-93-2
NM: Uric-Acid
AN: 92185391
UD: 9206
MEDLINE EXPRESS (R) 1990 108 of 122
TI: Lesch-Nyhan syndrome.
AU: Krolls-SO
AD: Department of Diagnostic Sciences, School of Dentistry, University of Mississippi Medical Center, Jackson.
SO: Miss-Dent-Assoc-J. 1990 Summer; 46(2): 24-5
ISSN: 0098-4329
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
MESH: Child-; Restraint,-Physical
MESH: *Lesch-Nyhan-Syndrome; *Self-Mutilation-prevention-and-control
TG: Case-Report; Human; Male
PT: JOURNAL-ARTICLE
AN: 92017520
UD: 9201
SB: DENTAL
MEDLINE EXPRESS (R) 1990 109 of 122
TI: A dopamine deficiency model of Lesch-Nyhan disease--the neonatal-6-OHDA-lesioned rat.
AU: Breese-GR; Criswell-HE; Duncan-GE; Mueller-RA
AD: Brain and Development Research Center, University of North Carolina, School of Medicine, Chapel Hill 27599.
SO: Brain-Res-Bull. 1990 Sep; 25(3): 477-84
ISSN: 0361-9230
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: Lesch-Nyhan syndrome is characterized by a deficiency of the enzyme hypoxanthine phosphoribosyl transferase (HPRT), compulsive self-mutilatory behavior (SMB), and a loss of central dopaminergic neurons. In order to model the loss of central dopamine-containing neurons in this developmental disorder, neonatal rat pups 3 days of age were given the neurotoxin 6-OHDA intracisternally to reduce brain dopamine. Accompanying the profound loss of dopamine produced by this treatment was an increase in striatal serotonin content. When these neonatally lesioned rats were challenged as adults with systemically administered L-DOPA or with muscimol administration into substantia nigra reticulata (SNR), SMB was observed, a response not observed in unlesioned rats. Thus, the neonatally lesioned rats exhibit increased susceptibility for SMB. Since a D1-dopamine antagonist blocked the SMB response to L-DOPA, it was proposed that D1-dopamine receptors were critical to this behavioral response. Basic investigations concerning D1-dopamine receptor mechanisms in the lesioned rats have been performed and these are reviewed. The data in the neonatally lesioned rats provide convincing evidence that the absence of central dopaminergic neurons is responsible for at least some of the neurological symptoms of the Lesch-Nyhan syndrome, a finding consistent with data collected in mice with an HPRT deficiency.
MESH: Hydroxydopamines-; Lesch-Nyhan-Syndrome-physiopathology; Rats-; Sympathectomy,-Chemical
MESH: *Animals,-Newborn-physiology; *Disease-Models,-Animal; *Dopamine-deficiency; *Lesch-Nyhan-Syndrome-chemically-induced
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: HD23042HDNICHD; NS21345NSNINDS; MH36294MHNIMH
RN: 0; 1199-18-4; 51-61-6
NM: Hydroxydopamines; Oxidopamine; Dopamine
AN: 91152541
UD: 9106
MEDLINE EXPRESS (R) 1990 110 of 122
TI: Purine synthesis de novo and salvage in hypoxanthine phosphoribosyltransferase-deficient mice.
AU: Allsop-J; Watts-RW
AD: Clinical Research Centre, Harrow, UK.
SO: Enzyme. 1990; 43(3): 155-9
ISSN: 0013-9432
PY: 1990
LA: ENGLISH
CP: SWITZERLAND
AB: Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficiency' syndrome) may be associated with minor neurological manifestations. Whole body purine synthesis de novo is accelerated in both these groups of patients. A strain of mice with an experimentally produced mutation at the HPRT locus showed some residual 'apparent HPRT activity' in brain, liver, testicular, splenic, kidney and ovarian tissues but not in erythrocyte haemolysates. The mutation removes exons 1 and 2 of the coding region of the gene together with the promotor and about 10 kb of upstream sequence from the gene. It is therefore possible that the observed 'apparent HPRT activity' in these mice is due to the operation of an alternative metabolic pathway. Purine synthesis de novo was markedly accelerated in their brain, testicular, splenic and kidney tissues. It was not accelerated in the liver tissue of male mice hemizygous for the mutation and the degree of acceleration in the female homozygotes only just reached statistical significance at the p = 0.02 level. This observation casts doubt on the importance of modulations in the rate of hepatic purine synthesis de novo as a mechanism for maintaining a steady supply of purines for translocation to other organs.
MESH: Adenine-Phosphoribosyltransferase-metabolism; Brain-enzymology; Gonads-enzymology; Homozygote-; Hypoxanthine-Phosphoribosyltransferase-genetics; Hypoxanthine-Phosphoribosyltransferase-metabolism; Kidney-enzymology; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-metabolism; Mice-; Mice,-Mutant-Strains; Mutation-; Spleen-enzymology
MESH: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Purines-metabolism
TG: Animal; Female; Male
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.7; EC 2.4.2.8; 0
NM: Adenine-Phosphoribosyltransferase; Hypoxanthine-Phosphoribosyltransferase; Purines
AN: 91249765
UD: 9109
MEDLINE EXPRESS (R) 1990 111 of 122
TI: Urinary calculi associated with purine metabolism. Uric acid nephrolithiasis.
AU: Williams-Larson-AW
AD: Division of Nephrology and Internal Medicine, Mayo Clinic, Rochester, Minnesota.
SO: Endocrinol-Metab-Clin-North-Am. 1990 Dec; 19(4): 821-38
ISSN: 0889-8529
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: Uric acid stones are the consequences of abnormalities in purine metabolism, urate/uric acid renal handling, or excess dietary protein. Treatment is aimed at preventing additional formation by decreasing the degree of urate and uric acid supersaturation in urine, by altering diet, fluid intake, and the urine pH, and by blocking steps in uric acid production.
MESH: Adenine-Phosphoribosyltransferase-deficiency; Kidney-Calculi-diagnosis; Lesch-Nyhan-Syndrome-diagnosis; Risk-Factors; Uric-Acid-metabolism; Urinary-Calculi-prevention-and-control; Xanthine-Oxidase-deficiency
MESH: *Purines-metabolism; *Urinary-Calculi-etiology
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-ACADEMIC
RN: EC 1.1.3.22; EC 2.4.2.7; 0; 69-93-2
NM: Xanthine-Oxidase; Adenine-Phosphoribosyltransferase; Purines; Uric-Acid
AN: 91184152
UD: 9107
MEDLINE EXPRESS (R) 1990 112 of 122
TI: Animal models of Lesch-Nyhan syndrome.
AU: Jinnah-HA; Gage-FH; Friedmann-T
AD: Department of Neurosciences, UCSD School of Medicine, La Jolla 92093.
SO: Brain-Res-Bull. 1990 Sep; 25(3): 467-75
ISSN: 0361-9230
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: In humans, deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) is associated with a disorder known as Lesch-Nyhan syndrome which includes severe neurobehavioral abnormalities. Several animal models which have been developed to examine the neurobiologic substrates of this disorder have suggested a role for abnormal function in purine/dopamine neurotransmission, but the relationship between HPRT-deficiency and these abnormalities remains unknown. Recently, HPRT-deficient mice have been produced which appear to have similar, though more subtle changes in brain dopamine function. These mice will be useful in elucidating the relationship between HPRT-deficiency and the neurological deficits observed in patients with this disorder.
MESH: *Disease-Models,-Animal; *Lesch-Nyhan-Syndrome-physiopathology
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 91152540
UD: 9106
MEDLINE EXPRESS (R) 1990 113 of 122
TI: Molecular analysis of mutation at the human hprt locus.
AU: Lambert-B; Andersson-B; He-SM; Hellgren-D; Marcus-S; Steen-AM
AD: Department of Clinical Genetics, Karolinska Institute, Stockholm, Sweden.
SO: Acta-Physiol-Scand-Suppl. 1990; 592: 85-92
ISSN: 0302-2994
PY: 1990
LA: ENGLISH
CP: ENGLAND
MESH: Base-Sequence; Cloning,-Molecular; DNA-genetics; Hypoxanthine-Phosphoribosyltransferase-biosynthesis; Lesch-Nyhan-Syndrome-genetics; Molecular-Sequence-Data; Polymerase-Chain-Reaction; T-Lymphocytes-enzymology
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Mutation-
TG: Animal; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 91096618
UD: 9104
MEDLINE EXPRESS (R) 1990 114 of 122
TI: Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome.
AU: Thompson-GN; Pacy-PJ; Watts-RW; Halliday-D
AD: Nutrition Research Group, Clinical Research Centre, Harrow, United Kingdom.
SO: Pediatr-Res. 1990 Sep; 28(3): 240-6
ISSN: 0031-3998
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Adolescence-; Adult-; Amino-Acids-blood; Growth-Disorders-etiology; Growth-Disorders-metabolism; Lesch-Nyhan-Syndrome-complications; Leucine-blood; Middle-Age; Phenylalanine-blood; Phenylketonuria-etiology
MESH: *Lesch-Nyhan-Syndrome-metabolism; *Phenylketonuria-metabolism; *Proteins-metabolism
TG: Female; Human; Male
PT: JOURNAL-ARTICLE
RN: 0; 3617-44-5; 7005-03-0
NM: Amino-Acids; Phenylalanine; Leucine
AN: 91044609
UD: 9102
MEDLINE EXPRESS (R) 1990 115 of 122
TI: Mutations affecting RNA splicing in man are detected more frequently in somatic than in germ cells.
AU: Rossi-AM; Thijssen-JC; Tates-AD; Vrieling-H; Natarajan-AT; Lohman-PH; van-Zeeland-AA
AD: MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands.
SO: Mutat-Res. 1990 Aug; 244(4): 353-7
ISSN: 0027-5107
PY: 1990
LA: ENGLISH
CP: NETHERLANDS
AB: The spectrum of DNA sequence alterations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of HPRTase-deficient T-lymphocytes isolated from the blood of healthy male donors was determined and compared with the spectrum found in patients suffering from genetic diseases (Lesch-Nyhan syndrome or gouty arthritis) associated with a mutation in the same gene. Most of the T-cell mutants still produced hprt mRNA which was converted into cDNA and used for DNA sequence analysis after amplification using the polymerase chain reaction (PCR). In 39% of the 31 analyzed T-cell mutants of normal donors 1 or 2 exons were completely or partially deleted from hprt mRNA, probably because of a mutation in a splice acceptor site. Among patients suffering from the Lesch-Nyhan syndrome or gouty arthritis, the class of splice mutations amounts only to 7%. These data suggest that carriers of splice mutations often do not show the characteristics of HPRTase deficiency associated with these genetic diseases, because correctly spliced hprt mRNA is still produced at a low level.
MESH: Base-Sequence; Germ-Cells-metabolism; Hypoxanthine-Phosphoribosyltransferase-genetics; Hypoxanthine-Phosphoribosyltransferase-metabolism; Molecular-Sequence-Data; Polymerase-Chain-Reaction; T-Lymphocytes-metabolism
MESH: *Arthritis,-Gouty-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-; *RNA-Splicing
TG: Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 90348693
UD: 9011
MEDLINE EXPRESS (R) 1990 116 of 122
TI: [Prenatal diagnosis of Lesch-Nyhan syndrome]
TO: Diagnostico prenatal del sindrome de Lesch-Nyhan.
AU: Mateos-Anton-F; Garcia-Puig-J; Ramos-Hernandez-T; Lopez-Jimenez-M; Romera-Menoyo-N
AD: Servicio de Bioquimica, Hospital La Paz, Universidad Autonoma, Madrid.
SO: Med-Clin-Barc. 1990 Apr 28; 94(16): 624-7
ISSN: 0025-7753
PY: 1990
LA: SPANISH; NON-ENGLISH
CP: SPAIN
AB: A pregnant woman with Lesch-Nyhan's syndrome (hypoxanthine-guanine-phosphoribosyltransferase, or HGPRT deficiency) requested antenatal diagnosis. HGPRT and adenine phosphoribosyltransferase (APRT) activities were measured in fetal erythrocytes by funiculocentesis in the 21st gestational week. HGPRT activity was lower than 0.01 mmol/h/Hb g (normal value 87.0 +/- 16.05 mmol/h/Hb g). APRT activity was increased (44.0 mmol/h/Hb g) as compared with that from 50 normal individuals (28.1 +/- 6.9 mmol/h/Hb g). Pregnancy was interrupted and the antenatal diagnosis of Lesch-Nyhan's syndrome was confirmed after delivery. In the 20th gestational week, amniotic fluid showed a marked increase if oxypurines (hypoxanthine, xanthine and uric acid) as compared with the values in 14 amniotic fluids from normal pregnancies and gestational age within 15-22 weeks. The present study illustrates the possibility to make the antenatal diagnosis of Lesch-Nyhan's syndrome by funiculocentesis . The previously unreported finding of a marked abnormality of oxypurine concentration in amniotic fluid represents a new outlook for the diagnosis of enzymatic defects of synthesis and degradation of purine nucleotides.
MESH: Adult-; Amniocentesis-; Amniotic-Fluid-analysis; English-Abstract; Family-Health; Hypoxanthines-analysis; Lesch-Nyhan-Syndrome-enzymology; Pedigree-; Pregnancy-; Prenatal-Diagnosis-methods; Uric-Acid-analysis; Xanthines-analysis
MESH: *Fetal-Diseases-diagnosis; *Lesch-Nyhan-Syndrome-diagnosis
TG: Case-Report; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 69-93-2
NM: Hypoxanthines; Xanthines; Uric-Acid
AN: 90339906
UD: 9011
MEDLINE EXPRESS (R) 1990 117 of 122
TI: Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures.
AU: Skopek-TR; Recio-L; Simpson-D; Dallaire-L; Melancon-SB; Ogier-H; O'Neill-JP; Falta-MT; Nicklas-JA; Albertini-RJ
AD: Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
SO: Hum-Genet. 1990 Jun; 85(1): 111-6
ISSN: 0340-6717
PY: 1990
LA: ENGLISH
CP: GERMANY,-WEST
AB: The frequency of hprt mutants in peripheral blood T-lymphocytes of two putative Lesch-Nyhan individuals and their parents was determined by a cell cloning assay to quantify the frequency of thioguanine-resistant mutants. The results confirmed the Lesch-Nyhan diagnosis and demonstrated that the mother has an elevated mutant frequency consistent with being heterozygous for an hprt mutation. Mass cultures of T-lymphocytes from both the children and their mother, as well as cultures of hprt mutant clones from the mother, were employed as sources of mRNA for cDNA sequence analysis. These hprt mutants show a single base substitution (T----C transition) at position 170 (exon 3). The predicted amino acid change is the substitution of threonine for methionine56. We have designated this new Lesch-Nyhan mutation hprtMontreal. The use of T-lymphocyte cultures allows rapid sequence analyses of hprt mutations, as well as family studies to define the origin of a particular mutation.
MESH: Adult-; Base-Sequence; Cells,-Cultured; Child-; DNA-analysis; Gene-Frequency; Heterozygote-; Karyotyping-; Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymerase-Chain-Reaction; RNA,-Messenger-isolation-and-purification
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-; *T-Lymphocytes-cytology
TG: Female; Human; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO13068807
RN: EC 2.4.2.8; 0; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; RNA,-Messenger; DNA
AN: 90292681
UD: 9010
MEDLINE EXPRESS (R) 1990 118 of 122
TI: Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families.
AU: Gibbs-RA; Nguyen-PN; Edwards-A; Civitello-AB; Caskey-CT
AD: Institute for Molecular Genetics, Howard Hughes Medical Institute, Houston, Texas.
SO: Genomics. 1990 Jun; 7(2): 235-44
ISSN: 0888-7543
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: The Lesch-Nyhan (LN) syndrome is a genetically lethal human neurological disease that results from mutations that inactivate the hypoxanthine phosphoribosyltransferase (HPRT) gene. The elucidation of the complete DNA sequence of the human HPRT gene locus has enabled the construction of multiple oligonucleotide primer sets for the simultaneous in vitro amplification of all nine HPRT exons. The multiplex polymerase chain reaction provides a facile assay for the detection of HPRT exon deletions and the reaction products can be analyzed by direct automated fluorescent DNA sequencing to identify subtle alterations in the gene. Alterations have been identified in the HPRT genes from 15 independent LN cases, and 10 LN family studies were performed. The sequencing method uses solid supports and is sufficiently simple and sensitive to be a favored approach for LN diagnosis. LN heterozygotes can be diagnosed without reference to the affected male. In addition, these procedures will be useful for somatic mutagenesis studies.
MESH: Base-Sequence; DNA-genetics; Genes-; Heterozygote-Detection; Molecular-Sequence-Data; Pedigree-; Polymerase-Chain-Reaction
MESH: *Chromosome-Deletion; *Exons-; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics
TG: Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK31428DKNIDDK
RN: EC 2.4.2.8; 9007-49-2
NM: Hypoxanthine-Phosphoribosyltransferase; DNA
AN: 90269813
UD: 9009
SI: GENBANK/M26434
MEDLINE EXPRESS (R) 1990 119 of 122
TI: A pitfall in the prenatal diagnosis of Lesch-Nyhan syndrome by chorionic villus sampling.
AU: Page-T; Broock-RL
AD: Department of Pediatrics, University of California, San Diego, La Jolla 92093.
SO: Prenat-Diagn. 1990 Mar; 10(3): 153-7
ISSN: 0197-3851
PY: 1990
LA: ENGLISH
CP: ENGLAND
AB: The ratio of the activities of catabolic enzymes such as 5'-nucleotidase and purine nucleoside phosphorylase to that of hypoxanthine-guanine phosphoribosyltransferase (HPRT) may be much higher in frozen or cultured chorionic villus cells than in cultured amniotic fluid cells, cultured fibroblasts, or red blood cells. Consequently, unless these catabolic activities are controlled the observed activity of HPRT may be greatly decreased, and a false diagnosis of Lesch-Nyhan syndrome may result. For a reliable diagnosis, the reaction products of HPRT must be protected from catabolism.
MESH: Adenine-Phosphoribosyltransferase-metabolism; Amniotic-Fluid-metabolism; Cells,-Cultured; Chorionic-Villi-metabolism; False-Positive-Reactions; Freezing-; Hypoxanthine-Phosphoribosyltransferase-metabolism; Pregnancy-; Preservation,-Biological
MESH: *Chorionic-Villi-Sampling; *Lesch-Nyhan-Syndrome-diagnosis
TG: Female; Human
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.7; EC 2.4.2.8
NM: Adenine-Phosphoribosyltransferase; Hypoxanthine-Phosphoribosyltransferase
AN: 90259937
UD: 9008
MEDLINE EXPRESS (R) 1990 120 of 122
TI: Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex.
AU: Hatanaka-T; Higashino-H; Woo-M; Yasuhara-A; Sugimoto-T; Kobayashi-Y
AD: Department of Pediatrics, Kansai Medical University, Osaka, Japan.
SO: Acta-Neurol-Scand. 1990 Feb; 81(2): 184-7
ISSN: 0001-6314
PY: 1990
LA: ENGLISH
CP: DENMARK
AB: We studied a case of Lesch-Nyhan syndrome with delayed onset of self-mutilation. Athetotic cerebral palsy and mental retardation were diagnosed at 1 year old, but the disease was not suspected until age 8 years when he began biting his lips and fingers. There was no obvious alteration of catecholamine in urine and CSF. We attempted to induce a series of blink reflexes by electric, mechanical and photic procedures. The R1 amplitude increased and the latency of the R2 shortened compared with controls. This shows that not only orbicularis motoneuron itself, but also uncrossed interneurons, are in a state of hyperexcitability. The contralateral R2 was poor which was in favour of hypoexcitability of the crossed interneurons at the brainstem. The significant large response was obtained by photic procedure which was in favour of hyperexcitability of the motoneurons. Therefore, it is demonstrated that a thorough examination of blink reflexes provides a useful method for examination of a state of the underlying neural activity.
MESH: Child-; Lesch-Nyhan-Syndrome-complications
MESH: *Blinking-; *Brain-Stem-physiopathology; *Interneurons-physiology; *Lesch-Nyhan-Syndrome-physiopathology; *Self-Mutilation-etiology
TG: Case-Report; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
AN: 90224570
UD: 9007
MEDLINE EXPRESS (R) 1990 121 of 122
TI: Hypoxanthine guanine phosphoribosyltransferase deficiency: nucleotide substitution causing Lesch-Nyhan syndrome identified for the first time among Japanese.
AU: Fujimori-S; Kamatani-N; Nishida-Y; Ogasawara-N; Akaoka-I
AD: Second Department of Internal Medicine, University of Teikyo, Tokyo, Japan.
SO: Hum-Genet. 1990 Apr; 84(5): 483-6
ISSN: 0340-6717
PY: 1990
LA: ENGLISH
CP: GERMANY,-WEST
AB: A previously undescribed nucleotide substitution at codon 51 (CGA to TGA) has been identified using the polymerase chain reaction technique in hypoxanthine guanine phosphoribosyltransferase (HPRT) cDNA; this is the first molecular evidence for a point mutation in a Japanese patient with Lesch-Nyhan syndrome. The present mutation is the 19th nucleotide substitution identified as a germ-line mutation at this locus and the second mutation generating a stop codon. The position of the nucleotide substitution is exactly the same as a previously described mutation HPRTToronto, indicating for the first time that nucleotide substitutions at the same position in the sequence of HPRT can generate different mutant alleles, one causing a partial deficiency and the other a complete deficiency. Although the type of nucleotide substitution is different between the two cases, a single base position has twice become the target of a mutation. However, the calculation of the probability of finding substitution mutations at the same base position in the coding region of hprt indicates that there is no evidence for the presence of a hot spot for substitution mutations in the human hprt germ line.
MESH: Adolescence-; Base-Sequence; Codon-; Japan-; Lesch-Nyhan-Syndrome-enzymology; Molecular-Sequence-Data; Polymerase-Chain-Reaction
MESH: *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Mutation-
TG: Case-Report; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8; 0
NM: Hypoxanthine-Phosphoribosyltransferase; Codon
AN: 90215757
UD: 9007
MEDLINE EXPRESS (R) 1990 122 of 122
TI: Preimplantation sexing and diagnosis of hypoxanthine phosphoribosyl transferase deficiency in mice by biochemical microassay.
AU: Monk-M; Handyside-A; Muggleton-Harris-A; Whittingham-D
AD: MRC Mammalian Development Unit, London, UK.
SO: Am-J-Med-Genet. 1990 Feb; 35(2): 201-5
ISSN: 0148-7299
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: Hypoxanthine phosphoribosyl transferase (HPRT)-deficient male embryos derived from heterozygous (carrier) female mice were diagnosed by biochemical microassay of X-chromosome-coded HPRT activity in a single cell taken from the 8-cell embryo or in 5-10 cells sampled from the blastocyst. In the latter procedure, carrier female blastocysts could also be distinguished from affected males, and normal males and females, as having intermediate HPRT activity in the sampled trophectoderm cells. During the assay procedures, the operated preimplantation embryos were cultured. They were then transferred, in batches as diagnosed, to recipient females. The resulting fetuses were sexed by gonad morphology and assayed for HPRT activity. All those identified as HPRT-negative embryos by biopsy at the 8-cell or blastocyst stages were indeed HPRT-negative males. The heterozygous females were also correctly identified by the trophectoderm biopsy procedure. The sex of an embryo can also be diagnosed by HPRT activity dosage in a single blastomere taken from 8-cell embryos from a normal mating and cultured for 12 hours before assay. Both X chromosomes are active in female morulae and the blastomeres sampled from female preimplantation embryos have twice the X-coded HPRT activity compared to those from the male embryos. The accuracy of this procedure for sexing was again verified by transfer of the putative male and putative female embryos into recipient females.
MESH: Disease-Models,-Animal; Fertilization-in-Vitro; Hypoxanthine-Phosphoribosyltransferase-metabolism; Mice-; Pregnancy-; Preimplantation-Phase
MESH: *Lesch-Nyhan-Syndrome-diagnosis; *Prenatal-Diagnosis; *Sex-Determination
TG: Animal; Female
PT: JOURNAL-ARTICLE
RN: EC 2.4.2.8
NM: Hypoxanthine-Phosphoribosyltransferase
AN: 90178179
UD: 9006