GM25541

GM25541 iPSC from Fibroblast

Description:

LESCH-NYHAN SYNDROME; LNS
HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1; HPRT1; HPRT

Affected:

Yes

Sex:

Male

Age:

9 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Protocols

Protocol PDF

Biopsy Source

Skin

Cell Type

Stem cell

Cell Subtype

Induced pluripotent stem cell

Transformant

Reprogrammed (Episomal)

Sample Source

iPSC from Fibroblast

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XY.arr[hg19](1-22)x2,(XY)x1

Species

Homo sapiens

Common Name

Human

Remarks

iPSC line derived from GM01662 Fibroblast by episomal reprogramming; 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. Genomic integration of episomal plasmid detected; however there was no expression of exogenous reprogramming factors. Researchers purchasing hiPSCs from the NIGMS Repository are responsible for any limited use label licenses (LULLs) applicable to the cell line purchased. The applicable LULL to this line is iPS Academia Japan, Inc..

Characterizations

Passage Frozen

Induced Pluripotent Stem Cell

The frozen cell line submitted to the Repository was recovered and expanded. The expanded line was evaluated for viability surface antigen expression and alkaline phosphatase activity. Pluripotency was assessed via embryoid body (EB) formation. Steady-state mRNA expression patterns of undifferentiated iPSC and EBs were determined via real-time PCR. Characterization data are included in the Certificate of Analysis.

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.

Phenotypic Data

Remarks

Publications

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