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.

DE GASPERI, R., GAMA SOSA, M.a., Battistini, S., Yeretsian, J., Raghavan, S., Zelnik, N., et al. (1996). Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene. NEUROLOGY, 47, 547-552.

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

BATTISTINI, STEFANIA;
1996

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.
DE GASPERI, R., GAMA SOSA, M.a., Battistini, S., Yeretsian, J., Raghavan, S., Zelnik, N., et al. (1996). Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene. NEUROLOGY, 47, 547-552.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/40645
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