Abstract 19832: De Novo Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Are Rare and Associated With Large Deletions

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with mutations in genes encoding the cardiac desmosome. Inheritance of ARVC is autosomal dominant, however patients frequently have no family history, raising the question of whether a mutation is de novo (first occurring in the patient) or has been inherited. Prevalence and characteristics of de novo mutations in ARVC have never been described. Hypothesis: We predicted de novo desmosomal mutations are rare. Methods: In a multinational ARVC registry we identified 172 index patients who 1) met 2010 Task Force Criteria, 2) had one or more pathogenic/likely pathogenic desmosomal variants, and 3) whose family had undertaken genetic cascade screening. Variants were classified based on American College of Medical Genetics and Genomics guidelines. Inheritance of variants was assessed by pedigree analysis. Haplotyping of microsatellite markers was conducted for 5 common PKP2 variants (c.2386T>C, c.1848C>A, c.397C>T, c.235C>T, c.214...