title: Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy.
abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare heart disorder characterized by myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, patient can present serious ventricular arrhythmias, heart failure, and even sudden cardiac death. Previous studies have revealed that the generation and development of ARVC are related to structural changes of desmosomes. To date, at least 5 genes associated with desmosomes have been identified in patients with ARVC, including Desmoplakin, Plakophilin 2, Desmoglein 2, Desmocollin 2, and Junction plakoglobin. In this study, we applied whole-exome sequencing to explore the potential causative gene in a Chinese family with suspicious ARVC. A novel missense mutation (c.1090 G > A/p.V364 M) of DSC2 was identified and co-segregated with the affected family members. This mutation leads to a substitution of valine by methionine and is predicted to be damaging by bioinformatics tools. In conclusion, our study not only expands the spectrum of DSC2 mutations and contributes to genetic counseling of families with ARVC but also improves the awareness of pathogenesis in Chinese patients with ARVC.
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China; Department of Cell Biology, The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
authors.forename: Ji-Shi
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Fan
authors.affiliation: Department of Cell Biology, The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Cell Biology, The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China. Electronic address: shirlesmile@csu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
mesh_terms: D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D044466:Asian People; D051187:Desmocollins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: C081561:DSC2 protein, human; D051187:Desmocollins