GM11852

GM11852 LCL from B-Lymphocyte

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

Yes

Sex:

Male

Age:

1 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

ASHKENAZI

Country of Origin

USA

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; pregnancy complicated by vaginal bleeding at 10 weeks, and by brief episode of false pregnancy at 6 months; uncomplicated full-term birth; hyperbilirubinemia as neonate; history of “behavioral” problems (colic, disinterest in toys, crying, rarely smiling, demanding parents’ attention); examination at 8 months of age revealed bilateral macular pallor with prominence of fovea centralis (cherry red spots), poor visual fixation, abnormal startle response, decreased language, and decreased motor development (decreased tone in upper extremities, increased tone at both ankles with sustained clonus); progressive encephalopathy; developmental milestones include: rolled from front to back at 3 months (did not roll from back to front), sat without support at 6.5 months (unable to get to sitting position by himself), able to hold objects at 8 months (does not actively reach for objects); deficient hexosaminidase A activity in blood; donor subject is homozygous for a 4 base pair duplication in exon 11 of the HEXA gene, c.1274_1277dupTATC (p.Tyr427Ilefs), resulting in a premature termination signal; see GM11853 Fibroblast and GM23937 iPSC.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

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

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

606869.0001; 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.

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 2

606869.0001; TAY-SACHS DISEASE

Identified Mutation

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

Sanchez JA, Pierce KE, Rice JE, Wangh LJ, Linear-after-the-exponential (LATE)-PCR: an advanced method of asymmetric PCR and its uses in quantitative real-time analysis. Proc Natl Acad Sci U S A101(7):1933-8 2004

PubMed ID: 14769930

Rajavel KS, Neufeld EF, Nonsense-mediated decay of human HEXA mRNA. Mol Cell Biol21(16):5512-9 2001

PubMed ID: 11463833