Sánchez-Valle R, Lladó A, Ezquerra M, Rey M J, Rami L, Molinuevo J L
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Barcelona, Spain.
Eur J Neurol. 2007 Dec;14(12):1409-12. doi: 10.1111/j.1468-1331.2007.01988.x.
The aim of this study was to describe a novel mutation in exon 8 of the presenilin gene (L286P) associated with early-onset autosomal dominant Alzheimer's disease (AD) and lobar haematomas. The proband was a woman who developed cognitive decline with predominant memory loss at the age of 35 years. The patient died at the age of 54 years and the neuropathological examination confirmed the diagnosis of AD. Three of her four siblings, one parent and one sibling of her parent had suffered from cognitive decline at ages between 35 and 42 years. Three of them also presented lobar haematomas. The neuropathological examination, available in one of them, disclosed the presence of severe amyloid angiopathy as the cause of the haematoma. The study of PSEN1 gene with single strand conformation polymorphism technique failed to show abnormalities suggestive of mutations. Direct sequencing disclosed the presence of a missense mutation in codon 286 (L286P) in the proband and her already affected descendent, which was absent in the healthy sibling. L286P is a novel mutation in PSEN1 that causes familial early-onset AD and brain haematomas related to amyloid angiopathy.
本研究的目的是描述早发性常染色体显性阿尔茨海默病（AD）和脑叶血肿相关的早老素基因第8外显子的一种新突变（L286P）。先证者是一名35岁出现以记忆力减退为主的认知功能衰退的女性。患者于54岁死亡，神经病理学检查确诊为AD。她的四个兄弟姐妹中有三个、她的一位父母以及她父母的一个兄弟姐妹在35至42岁之间出现了认知功能衰退。他们中的三人还出现了脑叶血肿。其中一人的神经病理学检查显示存在严重的淀粉样血管病，这是血肿的病因。采用单链构象多态性技术对PSEN1基因进行研究未发现提示突变的异常情况。直接测序显示先证者及其已患病的后代中第286密码子存在错义突变（L286P），而健康的兄弟姐妹中不存在该突变。L286P是PSEN1基因中的一种新突变，可导致家族性早发性AD以及与淀粉样血管病相关的脑血肿。
