GM01110

GM01110 Fibroblast

Description:

TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA

Affected:

Yes

Sex:

Male

Age:

10 MO (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

PENNSYLVANIA DUTCH

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Non-Jewish; electrophor shows absence of hex A band; consanguineous parents; synthesizes an altered a-chain polypeptide: N-glycosylated but not phosphorylated, secreted, or processed to mature form; donor subject is homozygous for a single nucleotide substitution from G to A at nucleotide 1444 in exon 13 of the HEXA gene (1444G>A) resulting in the substitution of lysine for glutamic acid at codon 482 [Glu482Lys (E482K)]

Characterizations

PDL at Freeze

5.87

Passage Frozen

MUTATION VERIFICATION

Nakano et al (J Neurochem 51:984-987 1988) performed sequence analysis of a clone containing the entire protein coding sequence of the Bhexosaminidase alpha chain from this Tay-Sachs disease patient. Their results showed a single nucleotide substitution from G to A at nucleotide residue no. 1444 which resulted in a change in amino acid residue no. 482 from the normal glutamic acid to lysine. Northern blotting analysis showed B-hexosaminidase alpha chain mRNA of apparently normal size and quantity.

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 1

606869.0004; TAY-SACHS DISEASE

Identified Mutation

GLU482LYS; Sequence analysis showed a single nucleotide substitution, from G to A, at nucleotide 1444, resulted in a change from glutamic acid to lysine at amino acid 482.

Gene

HEXA

Chromosomal Location

15q23-q24

Allelic Variant 2

606869.0004; TAY-SACHS DISEASE

Identified Mutation

GLU482LYS; Sequence analysis showed a single nucleotide substitution, from G to A, at nucleotide 1444, resulted in a change from glutamic acid to lysine at amino acid 482.

Phenotypic Data

Remarks

Publications

Chen Y1,2, Jian J1, Hettinghouse A1, Zhao X3, Setchell KDR3, Sun Y3, Liu CJ4,5, Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease J Mol Med96:1359-1373 2018

PubMed ID: 30341570

Nakano T, Muscillo M, Ohno K, Hoffman AJ, Suzuki K, A point mutation in the coding sequence of the beta-hexosaminidase alpha gene results in defective processing of the enzyme protein in an unusual GM2-gangliosidosis variant. J Neurochem51:984-7 1988

PubMed ID: 2970528

Ohno, Molecular genetics of B-N-acetyl-hexosaminidase alpha subunit mutations (from Lipid Storage Disorders, Plenum Publishing Corp) "Lipid Storage Disorders"1988, pp215:984-7 1988

PubMed ID: 2970528

Zokaeem G, Bayleran J, Kaplan P, Hechtman P, Neufeld EF, A shortened beta-hexosaminidase alpha-chain in an Italian patient with infantile Tay-Sachs disease. Am J Hum Genet40:537-47 1987

PubMed ID: 2954459

Proia RL, Neufeld EF, Synthesis of beta-hexosaminidase in cell-free translation and in intact fibroblasts: an insoluble precursor alpha chain in a rare form of Tay- Sachs disease. Proc Natl Acad Sci U S A79:6360-4 1982

PubMed ID: 6959123

Hasilik A, Neufeld EF, Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem255:4946-50 1980

PubMed ID: 6989822

Hasilik A, Neufeld EF, Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J Biol Chem255:4937-45 1980

PubMed ID: 6989821