Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Class Disorders of Nucleotide and Nucleic Acid Metabolism
Quantity 10 µg
Quantitation Method Please see our FAQ
Biopsy Source Arm
Cell Type Fibroblast
Tissue Type Skin
Transformant Untransformed
Race Caucasian
Family Member 1
Relation to Proband proband
Confirmation Clinical summary/Case history
Species Homo sapiens
Common Name Human
Remarks Clinically affected; no detectable HPRT and normal APRT activity; 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 GM06804 for Lymph of same subject; mother (GM01659) and sisters (GM01660/GM01661) are unaffected carriers.
Passage Frozen 7
 
MUTATION VERIFICATION Yang et al (Nature 310:412 1984) reported that northern blot analysis of RNA from this culture revealed a mutation that resulted in an aberrant HPRT mRNA of normal abundance that was approximately 250 nucleotides larger than wild-type HPRT mRNA. The mutation is a result of a duplication of exons 2 and 3 (Yang et al Somat Cell Mol Genet 14: 293 1988).
 
hypoxanthine phosphoribosyltransferase According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.4.2.8; 0% activity.
 
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by LINE assay
 
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.
Remark Clinically affected; no detectable HPRT and normal APRT activity; 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 GM06804 for Lymph of same subject; mother (GM01659) and sisters (GM01660/GM01661) are unaffected carriers.
Shammas MA, Koley H, Beer DG, Li C, Goyal RK, Munshi NC, Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor. Gastroenterology126(5):1337-46 2004
PubMed ID: 15131795
 
Shammas MA, Shmookler Reis RJ, Akiyama M, Koley H, Chauhan D, Hideshima T, Goyal RK, Hurley LH, Anderson KC, Munshi NC, Telomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma. Mol Cancer Ther2(9):825-33 2003
PubMed ID: 14555701
 
Hotamisligil GS, Breakefield XO, Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet49:383-92 1991
PubMed ID: 1678250
 
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
 
Caskey CT, Disease diagnosis by recombinant DNA methods. Science236:1223-9 1987
PubMed ID: 3296189
 
Gunby JL, Tomkins DJ, Chang PL, Somatic cell hybridization of Roberts syndrome and normal human fibroblasts transfected with plasmids carrying dominant selection markers. Somat Cell Mol Genet13:245-52 1987
PubMed ID: 3474785
 
Chang PL, Gunby JL, Tomkins DJ, Mak I, Rosa NE, Mak S, Transformation of human cultured fibroblasts with plasmids carrying dominant selection markers and immortalizing potential. Exp Cell Res167:407-16 1986
PubMed ID: 3021482
 
Boggs BA, Nussbaum RL, Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. Somat Cell Mol Genet10:607-13 1984
PubMed ID: 6095463
 
Drescher-Lincoln CK, Smith JR, Inhibition of DNA synthesis in senescent-proliferating human cybrids is mediated by endogenous proteins. Exp Cell Res153:208-17 1984
PubMed ID: 6734738
 
Yang TP, Patel PI, Chinault AC, Stout JT, Jackson LG, Hildebrand BM, Caskey CT, Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients. Nature310:412-4 1984
PubMed ID: 6087154
 
Nussbaum RL, Crowder WE, Nyhan WL, Caskey CT, A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci U S A80:4035-9 1983
PubMed ID: 6306659
 
Pereira-Smith OM, Smith JR, Evidence for the recessive nature of cellular immortality. Science221:964-6 1983
PubMed ID: 6879195
 
Pereira-Smith OM, Smith JR, Phenotype of low proliferative potential is dominant in hybrids of normal human fibroblasts. Somatic Cell Genet8:731-42 1982
PubMed ID: 7163953
 
James L, Veomett GE, Decreased longevity of human diploid cells after incorporation of latex spheres within their cytoplasm. Exp Cell Res132:468-73 1981
PubMed ID: 7215456
 
Pereira-Smith OM, Smith JR, Expression of SV40 T antigen in finite life-span hybrids of normal and SV40-transformed fibroblasts. Somatic Cell Genet7:411-21 1981
PubMed ID: 6269237
 
Schonberg S, German J, Sister chromatid exchange in cells metabolically coupled to Bloom's syndrome cells. Nature284:72-4 1980
PubMed ID: 7354874
View pedigree 
Passage Frozen 7
Split Ratio 1:3
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 15% fetal bovine serum Not inactivated
Substrate None specified
Subcultivation Method trypsin-EDTA