期刊
MOLECULAR GENETICS & GENOMIC MEDICINE
卷 4, 期 6, 页码 617-623出版社
WILEY
DOI: 10.1002/mgg3.245
关键词
Exome; false-positive variants; familial dilated cardiomyopathy; next-generation sequencing; NGS
资金
- Danish National Researched Foundation Centre for Cardiac Arrhythmia
- John and Birthe Meyer Foundation
- Research Foundation of the Heart Centre Rigshospitalet
Background Hundreds of genetic variants have been described as disease causing in dilated cardiomyopathy (DCM). Some of these associations are now being questioned. We aimed to identify the prevalence of previously DCM associated variants in the Exome Aggregation Consortium (ExAC), in order to identify potentially false-positive DCM variants. Methods Variants listed as DCM disease-causing variants in the Human Gene Mutation Database were extracted from ExAC. Pathogenicity predictions for these variants were mined from dbNSFP v 2.9 database. Results Of the 473 DCM variants listed in HGMD, 148 (31%) were found in ExAC. The expected number of individuals with DCM in ExAC is 25 based on the prevalence in the general population. Yet, 35 variants were found in more than 25 individuals. In 13 genes, we identified all variants previously associated with DCM; four genes contained variants above our estimated cut-off. Prediction tools found ExAC variants to be significantly more tolerated when compared to variants not found in ExAC (P = 0.004). Conclusion In ExAC, we identified a higher genotype prevalence of variants considered disease-causing than expected. More importantly, we found 13 genes in which all variants previously associated with DCM were identified in ExAC, questioning the association of these genes with the monogenic form of DCM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据