title: 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: Department of Neurology, New York University School of Medicine, NY 10016, USA.
authors: R
authors: R
authors: De Gasperi
authors: M A
authors: MA
authors: Gama Sosa
authors: S
authors: S
authors: Battistini
authors: J
authors: J
authors: Yeretsian
authors: S
authors: S
authors: Raghavan
authors: N
authors: N
authors: Zelnik
authors: E
authors: E
authors: Leshinsky
authors: E H
authors: EH
authors: Kolodny
mesh_terms: D000328:Adult; D017668:Age of Onset; D005260:Female; D005678:G(M2) Ganglioside / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D013661:Tay-Sachs Disease / Q000235:genetics*
chemical_list: D005678:G(M2) Ganglioside