GM03770

GM03770 LCL from B-Lymphocyte

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

Yes

Sex:

Male

Age:

15 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

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Jewish; variant; HEX A deficiency in white cells and lymphoblasts; mild dysarthria; 3 similarly affected sibs; 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 4 base pair insertion in exon 11 of the HEXA gene [1278_1279insTATC] resulting in a premature termination signal.

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.

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 (GM03770) 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.

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

606869.0001; 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

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

Gibbons WE, Gitlin SA, Lanzendorf SE, Strategies to respond to polymerase chain reaction deoxyribonucleic acid amplification failure in a preimplantation genetic diagnosis program. Am J Obstet Gynecol172:1088-95 1995

PubMed ID: 7726246

Gibbons WE, Gitlin SA, Lanzendorf SE, Kaufmann RA, Slotnick RN, Hodgen GD, Preimplantation genetic diagnosis for Tay-Sachs disease: successful pregnancy after pre-embryo biopsy and gene amplification by polymerase chain reaction. Fertil Steril63:723-8 1995

PubMed ID: 7890054

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