Description:
TAY-SACHS DISEASE; TSD
HEXOSAMINIDASE A; HEXA
Repository
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NIGMS Human Genetic Cell Repository
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Subcollection |
Heritable Diseases Lysosomal Storage Diseases GeT-RM Samples |
Class |
Disorders of Lipid Metabolism |
Quantity |
25 µg |
Quantitation Method |
Please see our FAQ |
Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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JEWISH
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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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GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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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. |
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MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
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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 |
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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. |
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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. |
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].
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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 |
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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 |
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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 |
dbSNP |
dbSNP ID: 10665 |
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 |
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