Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene.

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.

• 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)

Chemical References

• G(M2) Ganglioside

Topics

• Adult
• Age of Onset
• Female
• G(M2) Ganglioside (genetics)
• Humans
• Mutation
• Polymerase Chain Reaction
• Tay-Sachs Disease (genetics)