一个与常染色体显性阿尔茨海默病家族中的 logopenia、定向障碍和失用症相关的新型 V272D 早老素突变。

A novel V272D presenilin mutation associated with logopenia, disorientation, and apraxia in an autosomal-dominant Alzheimer's disease family.

机构信息

Chair of Geriatric Medicine, University Essen, and Geriatric Centre Haus Berge, Contilia Group, Essen, Germany; Department of Neurology, Philipps-University Marburg, Marburg, Germany; Laboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Laboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

Neurobiol Aging. 2020 Jan;85:154.e5-154.e7. doi: 10.1016/j.neurobiolaging.2019.07.002. Epub 2019 Aug 7.

DOI:10.1016/j.neurobiolaging.2019.07.002

PMID:31500908

Abstract

In the present study, a novel mutation in the presenilin 1 gene was discovered in an Iraq-native patient with early-onset Alzheimer's disease, who presented with speech impairment and memory decline at age 46 years. Magnetic resonance imaging showed a frontotemporal atrophy. Sanger sequencing identified a heterozygous T to A transversion at position 815 (c.815T>A) in the presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 272 from valine to aspartate (V272D). We tested this PSEN1 mutation in vitro and found V272D resulted in an altered Aβ42/40 ratio.

摘要

在本研究中，我们在一位伊拉克籍早发性阿尔茨海默病患者中发现了早老素 1 基因的一种新突变，该患者 46 岁时出现言语障碍和记忆力减退。磁共振成像显示额颞叶萎缩。桑格测序发现早老素 1 基因（PSEN1）第 815 位核苷酸由 T 突变为 A（c.815T>A），导致 272 位密码子由缬氨酸变为天冬氨酸（V272D）的新型错义突变。我们在体外检测了这种 PSEN1 突变，发现 V272D 导致 Aβ42/40 比值改变。