GM11853
Fibroblast from Skin, Thigh
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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Biopsy Source
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Thigh
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Thigh
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Race
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White
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Ethnicity
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ASHKENAZI
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Country of Origin
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USA
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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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| Passage Frozen |
2 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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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 |
606869.0001; 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. |
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| 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. |
| 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 in hands (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 GM11852 B-lymphocyte and GM23937 iPSC. |
| Colussi DJ, Jacobson MA, Patient-Derived Phenotypic High-Throughput Assay to Identify Small Molecules Restoring Lysosomal Function in Tay-Sachs Disease SLAS discovery : advancing life sciences R & D24:295-303 2019 |
| PubMed ID: 30616450 |
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| Soyombo AA, Tjon-Kon-Sang S, Rbaibi Y, Bashllari E, Bisceglia J, Muallem S, Kiselyov K, TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity The Journal of biological chemistry281:7294-301 2005 |
| PubMed ID: 16361256 |
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| Boles DJ, Proia RL, The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation. Am J Hum Genet56:716-24 1995 |
| PubMed ID: 7887427 |
| dbSNP |
dbSNP ID: 13779 |
| 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 |
2 |
| Split Ratio |
1:5 |
| 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 |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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