Description:
LESCH-NYHAN SYNDROME; LNS
HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1; HPRT1; HPRT
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| MUTATION VERIFICATION |
Yang et al (Nature 310:412 1984) reported that northern blot analysis of RNA from fibroblasts from this patient revealed a mutation that resulted in an aberrant HPRT mRNA of normal abundance that was approximately 250 nucleotides larger than wild-type HPRT mRNA. DNA from this culture was employed to show that the mutation is a result of a duplication of exons 2 & 3 (Yang et al Somat Cell Mol Genet 14:293 1988). |
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| hypoxanthine phosphoribosyltransferase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.4.2.8; 0% activity. |
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| Gene |
HPRT1 |
| Chromosomal Location |
Xq26-q27.2 |
| Allelic Variant 1 |
308000.0047; LESCH-NYHAN SYNDROME |
| Identified Mutation |
EX2-3DUP, IVS1DEL; In GM1662 and GM6804 from patients with LNS, Yang et al.(1984, 1988) found a complex rearrangement involving duplication of exons 2 and 3 and deletion of intron 1. Increased size of mRNA was observed. Monnat et al. (1992) demonstrated that the duplication in GM6804 was generated by the nonhomologous insertion of duplicated HPRT DNA into HPRT intron 1. They found that the duplication was genetically unstable and had a reversion rate approximately 100-fold higher than the rate of duplication formation. Exons 2 and 3, together with 13.7 kb of surrounding HPRT sequence, were duplicated.
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| Remarks |
Clinically affected; no detectable HPRT and normal APRT activity in fibroblasts; has an exon 2,3 duplication in the HPRT1 gene and a correspondingly elongated HPRT mRNA; atypical disease: lacks compulsive self-mutilation and mental retardation; see GM01662 for Fibro of same subject; mother (GM01659) and sisters (GM01660/GM01661) are unaffected carriers. |
| Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics: 2021 |
| PubMed ID: 35394024 |
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| Andrew M. Gross PhD, Subramanian S. Ajay PhD, Vani Rajan MS, Carolyn Brown CGC, Krista Bluske PhD, Nicole J. Burns MS, Aditi Chawla PhD, Alison J. Coffey PhD, Alka Malhotra PhD, Alicia Scocchia MS CGC, Erin Thorpe MS CGC, Natasa Dzidic MS, Karine Hovanes PhD FACMG, Trilochan Sahoo MD FACMG, Egor Dolzhenko PhD, Bryan Lajoie PhD, Amirah Khouzam MS CGC, Shimul Chowdhury PhD FACMG, John Belmont MD PhD, Eric Roller PhD, Sergii Ivakhno PhD, Stephen Tanner PhD, Julia McEachern PA MHS, Tina Hambuch PhD FACMG, Michael Eberle PhD, R. Tanner Hagelstrom PhD FACMG, David R. Bentley PhD, Denise L. Perry MS CGC & Ryan J. Taft PhD, Copy-number variants in clinical genome sequencing: deployment and interpretation for rare and undiagnosed disease Genetics in Medicine: 2018 |
| PubMed ID: 30293986 |
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| Yeeok Kang, Seong-Hyeuk Nam, Kyung Sun Park, Yoonjung Kim, Jong-Won Kim, Eunjung Lee, Jung Min Ko, Kyung-A Lee and Inho ParkEmail, DeviCNV: detection and visualization of exon-level copy number variants in targeted next-generation sequencing data BMC Bioinformatics19: 2018 |
| PubMed ID: 30326846 |
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| Jinnah HA, De Gregorio L, Harris JC, Nyhan WL, O'Neill JP, The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res463(3):309-26 2000 |
| PubMed ID: 11018746 |
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| Monnat RJ Jr, Chiaverotti TA, Hackmann AF, Maresh GA, Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications. Genomics13:788-96 1992 |
| PubMed ID: 1639405 |
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| Yang TP, Stout JT, Konecki DS, Patel PI, Alford RL, Caskey CT, Spontaneous reversion of novel Lesch-Nyhan mutation by HPRT gene rearrangement. Somat Cell Mol Genet14:293-303 1988 |
| PubMed ID: 2835825 |
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| Gibbs RA, Caskey CT, Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage. Science236:303-5 1987 |
| PubMed ID: 3563511 |
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