Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy

• Published in: The American journal of cardiology 2017-05, Vol.119 (9), p.1485-1489
• Main Authors: Liu, Ji-shi, M.D, Fan, Liang-liang, PH.D, Li, Jing-jing, B.S, Xiang, Rong, PH.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arrhythmogenic Right Ventricular Dysplasia - genetics; Asian Continental Ancestry Group; Bioinformatics; Cardiac arrhythmia; Cardiomyopathy; Cardiovascular; Catenin; Damage; Desmocollin; Desmocollins - genetics; Desmosomes; Exome - genetics; Family medical history; Female; Gene sequencing; Genes; Genetic counseling; Genetic screening; Heart; Heart diseases; Humans; Localization; Male; Methionine; Middle Aged; Missense mutation; Mutation; Mutation, Missense; NMR; Nuclear magnetic resonance; Pathogenesis; Patients; Pedigree; Sequence Analysis, DNA; Ultrasonic imaging; Valine; Ventricle
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2017.01.011

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 study 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 ARVC patients, 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.1090G>A/p.V364M) 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 ARVC patients.