GM03052

GM03052 Fibroblast

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

No Data

Sex:

Female

Age:

24 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Ethnicity

ASHKENAZI

Family Member

Relation to Proband

mother

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Ashkenazi; clinically unaffected; neither alpha chain allele has a splice junction mutation; 1 alpha chain allele has a 4 bp insertion in exon 11; mother of GM02968A

Characterizations

PDL at Freeze

4.38

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

MUTATION VERIFICATION

Myerowitz (Proc Natl Acad Sci USA 85:3955 1988) observed 2 normal alpha chain alleles with respect to the splice junction mutation observed in the spouse and affected child of this woman. Arpaia et al (NATURE 333:86-86 1988) reported that this Tay-Sachs disease heterozygote lacked the splice junction mutation a DdeI restriction site which was found in her husband and affected daughter (GM02968). Myerowitz and Costigan (J Biol Chem 263:18587-18589 1988) found that one alpha chain allele had a 4 base pair insertion in exon 11 which was the same as that found for one allele in her affected daughter. This lesion was found in approximately 70% of Tay-Sachs carriers in the Ashkenazi Jewish population.

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 1

606869.0001; TAY-SACHS DISEASE

Identified Mutation

c.1274_1277dupTATC; Myerowitz and Costigan [J Biol Chem 263: 18587 (1988)] demonstrated that the most frequent DNA lesion in Tay-Sachs disease of Ashkenazi Jews is a 4-bp insertion in exon 11. This mutation introduces a premature termination signal in exon 11, resulting in a deficiency of mRNA. This is the most frequent defect underlying Tay-Sachs disease in the Ashkenazi Jewish population. This mutation is alternatively designated 1277TATC; see 272800.0054.

Phenotypic Data

Remarks

Ashkenazi; clinically unaffected; neither alpha chain allele has a splice junction mutation; 1 alpha chain allele has a 4 bp insertion in exon 11; mother of GM02968A

Publications

Boles DJ, Proia RL, The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation. Am J Hum Genet56:716-24 1995

PubMed ID: 7887427

Arpaia E, Dumbrille-Ross A, Maler T, Neote K, Tropak M, Troxel C, Stirling JL, Pitts JS, Bapat B, Lamhonwah AM, et al, Identification of an altered splice site in Ashkenazi Tay-Sachs disease. Nature333:85-6 1988

PubMed ID: 3362213

Myerowitz R, Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: evidence against a single defect within this ethnic group. Proc Natl Acad Sci U S A85:3955-9 1988

PubMed ID: 3375249

Myerowitz R, Costigan FC, The major defect in Ashkenazi Jews with Tay-Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase. J Biol Chem263:18587-9 1988

PubMed ID: 2848800