国家神经系统疾病临床医学研究中心数据管理与共享系统

Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases

《国家中心数据管理与共享系统操作说明书 —— 研究者部分》

Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease

第一作者：Wang Guihong,Zhang Deng-Feng,Jiang Hong-Yan

通讯作者：Shan Baoci,Yao Yong-Gang,Feng Tao

Alzheimer's disease; Association; Dementia; Mutati

基本信息

2019-06-01

已发表文章

发表杂志：Journal of Psychiatric Research

发表类型: Research Article

影响因子(IF): 4.791

PMID: 30954774 Pubmed原文链接 全文下载

主要研究背景及目的

方法

In this study, we analyzed the mutation pattern of dementia-causal genes in 169 Han Chinese patients with familial and early-onset AD by using whole exome sequencing or targeted resequencing. We identified 9 potentially pathogenic mutations in the AD-causal genes APP, PSEN1, PSEN2, and 6 mutations in a group of non-AD dementia-causal genes including the FTD-causal gene GRN and the VaD-causal gene NOTCH3.

结论

These mutations also support the idea that there are overlapping pathomechanisms between AD and other forms of dementia.

主要结果

A common splice-site variant rs514492 in the FTD-causal gene VCP showed a positive association with AD risk (P = 0.0003, OR = 1.618), whereas the rare missense variant rs33949390 (p. R 1628P) in the LBD-causal gene LRRK2 showed a protective effect on AD risk (P = 0.0004, OR = 0.170). The presence of putative pathogenic mutations and risk variants in these causal genes for different types of dementia in clinically diagnosed familial and early-onset AD patients suggests a need to screen for mutations of the dementia-causal genes in cases of AD to avoid misdiagnosis.