Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease
First author：Wang Guihong,Zhang Deng-Feng,Jiang Hong-Yan
Corresponding author：Shan Baoci,Yao Yong-Gang,Feng Tao
essential_information
- Person in charge：Wang Guihong,Zhang Deng-Feng,Jiang Hong-Yan
- Data Sources： OTHERS
- Number of papers：OTHERS20190806
- Published time：2019-06-01
2019-06-01
Published articles
Journal：Journal of Psychiatric Research
Publication type: Research Article
IF(IF): 4.791
PMID: 30954774 Link To Pubmed Full text Download
Background And Purpose
Method
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.
Conclusion
These mutations also support the idea that there are overlapping pathomechanisms between AD and other forms of dementia.
Main results
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.