Palmer M S, Beck J A, Campbell T A, Humphries C B, Roques P K, Fox N C, Harvey R, Rossor M N, Collinge J
Molecular Genetics, Biomedical Sciences Division, Imperial College School of Medicine, London, UK.
Hum Mutat. 1999;13(3):256. doi: 10.1002/(sici)1098-1004(1999)13:3<256::aid-humu11>3.0.co;2-p.
Familial Alzheimer's disease (AD) is an autosomal dominant disorder characterized by memory impairment and multiple cognitive deficits which occurs in mid to late life. Early onset AD has been associated with mutations in three genes, of which presenilin 1 (PS1) mutations are the most frequent. We sequenced the open reading frame from genomic DNA of a series of 21 early onset AD (AD3) UK families in which there were at least two affected individuals in two or more generations with a diagnosis of probable or definite AD. We found PS1 mutations in six of these families with no sequence variation in the remaining 15. The six families contained between them five different mutations of which two, I143F and P436S, have not been found elsewhere. I143F shows incomplete penetration within the affected family. P436S is the most carboxy-terminal presenilin 1 mutation reported to date.
家族性阿尔茨海默病（AD）是一种常染色体显性疾病，其特征为记忆障碍和多种认知缺陷，发病于中年后期。早发性AD与三个基因的突变有关，其中早老素1（PS1）突变最为常见。我们对来自21个英国早发性AD（AD3）家系的基因组DNA的开放阅读框进行了测序，这些家系中至少有两代的两个或更多受影响个体被诊断为可能或确诊的AD。我们在其中6个家系中发现了PS1突变，其余15个家系未发现序列变异。这6个家系共有5种不同的突变，其中两种，即I143F和P436S，在其他地方尚未发现。I143F在受影响的家系中表现出不完全外显率。P436S是迄今为止报道的最靠近羧基末端的早老素1突变。
