Abstract |
Late-onset GM2 gangliosidosis is a variant form of Tay-Sachs disease characterized by onset of symptoms and signs in adolescence or in early adult life. The deficiency of beta-hexosaminidase A ( Hex A) in this form of GM2 gangliosidosis has been invariably associated with the presence of the Gly269-->Ser substitution in the alpha-chain. We found two siblings of Ashkenazi Jewish descent diagnosed with late-onset GM2 gangliosidosis who were negative for the Gly269-->Ser mutation. Analysis of the HEXA gene showed that they were compound heterozygotes for the functionally silent 4-bp insertion in exon 11, typical of the infantile form of the disease and for a novel mutation, T538-->C, resulting in the missense Tyr180-->His. Expression studies in COS-7 cells suggested that the effect of this mutation was to decrease the stability of the alpha-chain at physiologic temperatures and therefore to indirectly affect the formation of mature Hex A.
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Authors | R De Gasperi, M A Gama Sosa, S Battistini, J Yeretsian, S Raghavan, N Zelnik, E Leshinsky, E H Kolodny |
Journal | Neurology
(Neurology)
Vol. 47
Issue 2
Pg. 547-52
(Aug 1996)
ISSN: 0028-3878 [Print] United States |
PMID | 8757036
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Age of Onset
- Female
- G(M2) Ganglioside
(genetics)
- Humans
- Mutation
- Polymerase Chain Reaction
- Tay-Sachs Disease
(genetics)
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