由β-淀粉样前体蛋白基因第717密码子突变引起的早发性阿尔茨海默病。

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.

作者信息

Chartier-Harlin M C, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J

机构信息

Department of Biochemistry, St Mary's Hospital Medical School, Imperial College, London, UK.

出版信息

Nature. 1991 Oct 31;353(6347):844-6. doi: 10.1038/353844a0.

DOI:10.1038/353844a0

PMID:1944558

Abstract

A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

摘要

已发现β-淀粉样前体蛋白基因第717密码子处的一个突变与一个家族性阿尔茨海默病家族共分离。在约100个受阿尔茨海默病多重影响的家族中，另外还有5个家族报告了这种突变。我们鉴定出了另一个家族F19，在这个家族中我们检测到β-淀粉样前体蛋白基因与阿尔茨海默病之间存在连锁关系。对该家族中受影响个体的第17外显子进行直接测序，发现一个碱基变化导致第717密码子处也发生了缬氨酸→甘氨酸的替换。第717密码子处与阿尔茨海默病表型相关的第二个等位基因变体的出现支持了它们是致病突变这一假说。