title: Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing.
abstract: Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease.
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Genomic Medical Institute, Wenzhou Medical University, Wenzhou, P. R. China.
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Nanjing General Hospital of Nanjing Military Command, P. R. China.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Ren
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Genomic Medical Institute, Wenzhou Medical University, Wenzhou, P. R. China.|Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, P. R. China.
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.affiliation: ZhongDa Hospital, Southeast University, Nanjing, P. R. China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Dai
mesh_terms: D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D002681:China; D030541:Databases, Genetic; D059472:Exome / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps; D012518:Sarcomeres / Q000235:genetics*; D017422:Sequence Analysis, DNA