Whole-Exome Sequencing Identified a Novel Desmoglein-2 Gene Mutation Associated with Familial Arrhythmogenic Right Ventricular Cardiomyopathy

Objective: The objective of this study is to evaluate novel variations in a Chinese family of Han ethnicity, with arrhythmogenic right ventricular cardiomyopathy (ARVC) by the powerful technology of whole-exome sequencing (WES). Methods: Genomic DNA from representative family members was extracted and processed for WES via standardized methods. The exome sequence data were analyzed by Genome Analysis Toolkit software. Sanger sequencing was performed on DNA from the proband for genotype confirmation and from the other family members for familial co-segregation analysis. Results: A rare single nucleotide variant c.1592T>G (p.Phe531Cys) in exon 10 of desmoglein-2 (DSG2) was identified by WES in the affected individuals but not in the healthy control, which was confirmed by Sanger sequencing, suggesting that the mutation probably was a causal mutation for the familial disorder of ARVC. Conclusion: We identified a rare disease-causing mutation of the DSG2 gene associated with familial ARVC. The results might contribute to the early genetic analysis in inherited cardiomyopathies.