GM03575

GM03575 LCL from B-Lymphocyte

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

Yes

Sex:

Female

Age:

31 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Alternate IDs

GM17362 [TAY-SACHS DISEASE; TSD]

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

ASHKENAZI

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Ashkenazi; ataxia, dementia, peripheral neuropathy; deficient HEX A; variant; guanosine to adenosine transition at the 3' end of exon 7 [Gly269Ser (G269S)] in 1 allele and a 4 base pair insertion in exon 11 in the other allele (1278insTATC)

Characterizations

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227.

MUTATION VERIFICATION

Paw et al (Proc Natl Acad Sci USA 86:2413-2417 1989) reported that a patient with adult-onset GM2 gangliosidosis had a substitution of a serine for glycine at position 269 of the alpha-subunit of B-hexosaminidase. This guanosine to adenosine transition at the 3 prime end of exon 7 causes a loss of a ScrFI restriction site. DNA from the lymphoblasts of this patient (GM03575) also showed the loss of the ScrFI restriction site. The other allele was found to have the 4 base pair insertion in exon 11 observed in some cases of infantile Tay-Sachs Disease.

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

beta-N-acetylhexosaminidase (hexosaminidase A)

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.52

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 1

606869.0008; GM2-GANGLIOSIDOSIS, ADULT ONSET

Identified Mutation

GLY269SER; In 8 Ashkenazi adult GM2 gangliosidosis patients from 5 different families, Navon and Proia [Science 243: 1471 (1989)] identified a G-to-A substitution at the 3-prime end of exon 7, resulting in the substitution of serine for glycine at position 269.

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 2

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

Publications

Paw BH, Kaback MM, Neufeld EF, Molecular basis of adult-onset and chronic GM2 gangliosidoses in patients of Ashkenazi Jewish origin: substitution of serine for glycine at position 269 of the alpha-subunit of beta-hexosaminidase [published erratum appears in Proc Natl Acad Sci U S A 1989 Jul;86(14):5625] Proc Natl Acad Sci U S A86:2413-7 1989

PubMed ID: 2522660