GM20392

GM20392 Fibroblast from Skin, Unspecified

Description:

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

Affected:

Yes

Sex:

Male

Age:

23 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; variant, hyperuricemia with neurologic symptoms; at 6 months patient began to have repeated fevers and appeared to have psychomotor retardation; at 18 months he was hospitalized for hypotonia and could not sit or stand by himself, could lift his head in the prone position but had no words; uric acid crystals were found in diapers and the concentration of serum uric acid was elevated; he had athetoid movements and developed dysarthric speech; over the next 18 months he learned to sit and stand with support and to swallow solid food; his intelligence appeared appropriate for his age; treated with allopurinol at age 11 years; never self-mutilated; finished high school at age 18 years; at age 20 years he was of normal height, had normal muscular development and could move about independently using a wheelchair or walk with assistance; when passively listening, he was able to control his choreoathetosis, but his neurologic abnormality became obvious as soon as he talked or moved; dysarthric speech; sparse hair making him appear older than his chronologic age; outgoing personality; one normal sister and one sister with heterozygous HPRT levels in hair root; affected maternal uncle; donor subject is hemizygous for a T>G transversion at nucleotide 23 in exon 1 of the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene [23T>G] resulting in a substitution of glycine for valine at codon 8 [Val8Gly (V8G)].

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

HPRT1

Chromosomal Location

Xq26-q27.2

Allelic Variant 1

V8G; LESCH-NYHAN SYNDROME

Identified Mutation

VAL8GLY

Phenotypic Data

Remarks

Publications

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

Sege-Peterson K, Chambers J, Page T, Jones OW, Nyhan WL, Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency. Hum Mol Genet1(6):427-32 1992

PubMed ID: 1301916

Bakay B, Nissinen E, Sweetman L, Francke U, Nyhan WL, Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome. Pediatr Res13(12):1365-70 1979

PubMed ID: 523196