Dumanchin C, Brice A, Campion D, Hannequin D, Martin C, Moreau V, Agid Y, Martinez M, Clerget-Darpoux F, Frebourg T
Laboratoire de Génétique Moléculaire, CHU de Rouen, France.
J Med Genet. 1998 Aug;35(8):672-3. doi: 10.1136/jmg.35.8.672.
The presenilin 1 (PS1) gene, located on chromosome 14, is the major gene involved in the autosomal dominant forms of early onset Alzheimer's disease (AD). In order to estimate the frequency of de novo PS1 mutations, we have sequenced the PS1 open reading frame in 13 clinically diagnosed patients with no affected relatives, who had developed AD before the age of 50. In one case with onset at 37 years, we identified a missense mutation resulting in a methionine to lysine substitution at codon 139 of the PS1 gene. This substitution is the fourth identified at the same codon. This study, in agreement with previous reports, suggests that de novo PS1 mutations can occur but at a low frequency.
位于14号染色体上的早老素1（PS1）基因，是早发性阿尔茨海默病（AD）常染色体显性遗传形式的主要相关基因。为了估计新发PS1突变的频率，我们对13例临床诊断为AD且无患病亲属、发病年龄在50岁之前的患者的PS1开放阅读框进行了测序。在1例37岁起病的患者中，我们鉴定出一个错义突变，该突变导致PS1基因第139密码子处的甲硫氨酸被赖氨酸替代。这种替代是在同一密码子处鉴定出的第四种情况。这项研究与先前的报道一致，表明新发PS1突变可能会发生，但频率较低。
