SCN5A and Brugada syndrome: While Brugada syndrome is associated most predominantly with loss-of-function mutations in the SCN5A gene (Figure 4), ARVC is a genetic myocardial disorder and most commonly associated with mutations in the PKP2 gene encoding the desmosomal protein plakophilin-2 (PKP2], causing loss of integrity of the desmosome and disruption of structural coupling between adjacent cardiomyocytes [128,129,130].