GM03461

GM03461 LCL from B-Lymphocyte

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

Yes

Sex:

Male

Age:

24 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples

Class

Disorders of Lipid Metabolism

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

JEWISH

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Ashkenazi; variant; deficient hexosaminidase A; weakness and ataxia; donor subject is a compound heterozygote: one allele has a G>A transition at nucleotide 805 in exon 7 of the HEXA gene [805G>A] resulting in a substitution of serine for glycine at codon 269 [Gly269Ser (G269S)] and a second allele has a splice site mutation with a G>C transversion in the first nucleotide of intron 12 [IVS12+1G>C].

Characterizations

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

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

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

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 quanosine 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 (GM03461) also showed the loss of the ScrFI restriction site. The other allele was found to have the intron 12 guanosine to cytidine splice-site mutation observed in some cases of infantile Tay-Sachs Disease.

MUTATION VERIFICATION

The gene mutation(s) in this sample have been verified by 6 laboratories.

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

606869.0002; TAY-SACHS DISEASE

Identified Mutation

IVS12DS, G>C, +1; Arpaia et al. [Nature 333: 85 (1988)] identified a single-base mutation in a cloned fragment of the HEXA gene from an Ashkenazi Jewish patient with Tay-Sachs disease. The change, a G-to-C substitution in the first nucleotide of intron 12, was expected to result in defective splicing of the mRNA. A test for the mutant allele based on amplification of DNA by the PCR and cleavage of a DdeI restriction site generated by the mutation showed that this case. This mutation, the second most frequent among Ashkenazi Jews, accounts for approximately 13% of cases in this ethnic group.

Phenotypic Data

Remarks

Publications

Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009

PubMed ID: 19815695

Paw BH, Wood LC, Neufeld EF, A third mutation at the CpG dinucleotide of codon 504 and a silent mutation at codon 506 of the HEX A gene. Am J Hum Genet48:1139-46 1991

PubMed ID: 1827944

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