Description:
TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Lipid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Ethnicity
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PENNSYLVANIA DUTCH
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
5.87 |
| Passage Frozen |
9 |
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| 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. |
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| 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. |
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| 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. |
| 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)] |
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Hasilik A, Neufeld EF, Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem255:4946-50 1980 |
| PubMed ID: 6989822 |
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| 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 |
| dbSNP |
dbSNP ID: 21426 |
| Gene Cards |
HEXA |
| Gene Ontology |
GO:0004563 beta-N-acetylhexosaminidase activity |
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GO:0005764 lysosome |
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GO:0005975 carbohydrate metabolism |
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GO:0006687 glycosphingolipid metabolism |
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GO:0016798 hydrolase activity, acting on glycosyl bonds |
| NCBI Gene |
Gene ID:3073 |
| NCBI GTR |
272800 TAY-SACHS DISEASE; TSD |
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606869 HEXOSAMINIDASE A; HEXA |
| OMIM |
272800 TAY-SACHS DISEASE; TSD |
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606869 HEXOSAMINIDASE A; HEXA |
| Omim Description |
B VARIANT GM2 GANGLIOSIDOSIS |
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GM2-GANGLIOSIDOSIS, ADULT CHRONIC TYPE, INCLUDED |
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GM2-GANGLIOSIDOSIS, TYPE I |
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HEXA DEFICIENCYHEXOSAMINIDASE A, INCLUDED; HEXA, INCLUDED |
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HEXOSAMINIDASE A DEFICIENCY |
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HEXOSAMINIDASE A DEFICIENCY, ADULT TYPE, INCLUDED |
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TAY-SACHS DISEASE, JUVENILE, INCLUDED |
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TAY-SACHS DISEASE, PSEUDO-AB VARIANT, INCLUDED |
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TAY-SACHS DISEASE, VARIANT B1, INCLUDED |
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TAY-SACHS DISEASE; TSD |
| Passage Frozen |
9 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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