Abstract 19270: Large Genomic Rearrangements of Desmosomal Genes in Arrhythmogenic Cardiomyopathy

Introduction: Arrhythmogenic Cardiomyopathy (AC) is an inherited heart muscle disease associated with point mutations in genes encoding mainly components of the cardiac desmosome. Hypothesis: Since conventional mutation screening fails to uncover approximately 50% of AC genetic variants, we aimed to assess the prevalence of copy number variants (CNVs) involving desmosomal genes in a large cohort of unrelated genotype negative AC index cases and evaluated the pathogenic role of these CNVs by family co-segregation. Methods: 160 AC genotype negative probands for 5 AC-associated genes underwent Multiplex Ligation-dependent Probe Amplification (MLPA) and sequencing on a ABI 3500 (Thermoscientific). MLPA detected CNVs were further confirmed by quantitative Real-Time polymerase chain reaction on a Light Cycler 480 (Roche) and additional point mutations were excluded in other AC-related genes by targeted re-sequencing on a MiSeq platform (Illumina). Results: CNVs analysis revealed 4 different plakophilin-2 (PKP2)...