Screening for Genetic Mutations Associated with Early-Onset Alzheimer's Disease in Han Chinese

被引：1

作者：

Liu, Cuicui ^{[1
,2
,3
]}

Cong, Lin ^{[2
,3
]}

Zhu, Min ^{[2
,3
]}

Wang, Yongxiang ^{[2
,3
]}

Tang, Shi ^{[2
,3
]}

Han, Xiaojuan ^{[2
,3
]}

Zhang, Qinghua ^{[2
,3
]}

Tian, Na ^{[2
,3
]}

Liu, Keke ^{[2
,3
]}

Liang, Xiaoyan ^{[1
,3
]}

Fa, Wenxin ^{[2
,3
]}

Wang, Nan ^{[1
,3
]}

Hou, Tingting ^{[1
,2
,3
,4
]}

Du, Yifeng ^{[1
,2
,3
,4
]}

机构：

[1] Shandong Univ, Shandong Prov Hosp, Dept Neurol, Jinan, Shandong, Peoples R China

[2] Shandong First Med Univ, Shandong Prov Hosp, Dept Neurol, Jinan, Shandong, Peoples R China

[3] Shandong Prov Clin Res Ctr Neurol Dis, Jinan, Shandong, Peoples R China

[4] Shandong Univ, Shandong Prov Hosp, Dept Neurol, 324 Jing Wu Wei Qi Rd, Jinan 250021, Shandong, Peoples R China

来源：

CURRENT ALZHEIMER RESEARCH | 2022年 / 19卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Early-onset Alzheimer's disease; genetic mutations; whole-exome sequencing; A beta-centered network; neurology; genetic variants; APP; PSEN1; DEMENTIA;

D O I：

10.2174/1567205020666221028112915

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background:Early-onset Alzheimer's disease (EOAD) is highly influenced by genetic factors. Numerous mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1 and PSEN2) have been identified for EOAD, but they can only account for a small proportion of EOAD cases. Objective:This study aimed to screen genetic mutations and variants associated with EOAD among Han Chinese adults. Methods:This study included 34 patients with EOAD and 26 controls from a population-based study and neurological ward. We first sequenced mutations in APP/PSENs and then performed whole-exome sequencing in the remaining patients with negative mutations in APP/PSENs to screen for additional potential genetic variants. Among patients who were negative in genetic screening tests, we further evaluated the risk burden of genes related to the A beta metabolism-centered network to search for other probable causes of EOAD. Results:We identified 7 functional variants in APP/PSENs in 8 patients, including 1 APP mutation (p. Val715Met), 3 PSEN1 mutations (p. Phe177Ser; p. Arg377Met; p. Ile416Thr), and 3 PSEN2 mutations (p. Glu24Lys; p. Gly34Ser; p. Met239Thr). Of the remaining 26 EOAD cases without mutations in APP/PSENs, the proportion of carrying rare variants of genes involved in A beta and APP metabolism was significantly higher than that of controls (84.6% vs. 73.1%, P=0.042). Thirty-one risk genes with 47 variants were identified in 22 patients. However, in 26 normal subjects, only 20 risk genes with 29 variants were identified in 19 subjects. Conclusions:Our findings demonstrate the role of APP/PSENs mutations in EOAD, identifying a new PSEN2 missense mutation, and further offer valuable insights into the potential genetic mechanisms of EOAD without APP/PSENs mutations among Han Chinese.

引用

页码：724 / 733

页数：10

共 32 条

[1] Unusual phenotypic alteration of β amyloid precursor protein (βAPP) maturation by a new Val-715→Met βAPP-770 mutation responsible for probable early-onset Alzheimer's disease [J].