Late-onset G(m2) gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr(180)->His) in the Hex A alpha-chain gene

被引：20

作者：

DeGasperi, R ^{[1
]}

Sosa, MAG ^{[1
]}

Battistini, S ^{[1
]}

Yeretsian, J ^{[1
]}

Raghavan, S ^{[1
]}

Zelnik, N ^{[1
]}

Leshinsky, E ^{[1
]}

Kolodny, EH ^{[1
]}

机构：

[1] NYU, SCH MED, DEPT NEUROL, NEW YORK, NY 10016 USA

来源：

NEUROLOGY | 1996年 / 47卷 / 02期

关键词：

D O I：

10.1212/WNL.47.2.547

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Late-onset G(M2) 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 G(M2) gangliosidosis has been invariably associated with the presence of the Gly(269) --> Ser substitution in the alpha-chain. We found gangliosidosis who were negative for the two siblings of Ashkenazi Jewish descent diagnosed with late-onset G(M2) Gly(269) --> 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, T-538 --> C, resulting in the missense Tyr(180) --> His. Expression studies in COS-7 cells suggested that the effect of this mutation was to decrease the stability of the a-chain at physiologic temperatures and therefore to indirectly affect the formation of mature Hex A.

引用

页码：547 / 552

页数：6

共 27 条

[11]

HASILIK A, 1980, J BIOL CHEM, V255, P4937

[12] TAY-SACHS-DISEASE - CARRIER SCREENING, PRENATAL-DIAGNOSIS, AND THE MOLECULAR ERA - AN INTERNATIONAL PERSPECTIVE, 1970 TO 1993 [J].