Mutations of plakophilin-2 in Chinese with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart muscle disease associated with increased risks of sudden death, particularly in young, otherwise healthy, patients. The pathologic features are progressive myocardial atrophy and fibrofatty replacement. Plakophilin-2 (PKP2) is reported as the most common ARVD/C-causing gene in Western countries. In this study we aimed to determine the prevalence of PKP2 mutations in Chinese patients with ARVD/C and their phenotype characteristics. Genotype and phenotype were investigated in a cohort of 18 unrelated Chinese patients with a clinical diagnosis of ARVD/C. Direct sequencing of PKP2 led to the identification of 5 novel heterozygous mutations (R158K, Q211X, L419S, A793D, and N852fsX930) in 39% of patients (7 of 18) with ARVD/C. Among them, N852fsX930 was found in 3 unrelated young patients who presented with symptomatic ventricular tachyarrhythmia. Nevertheless, no significant difference could be detected between patients with ARVD/C with (n = 7) and without (n = 11) PKP2 mutations with regard to the phenotype characteristics and clinical outcomes. Decreased penetrance was prominent in family members. In conclusion, 5 novel PKP2 mutations were identified in a cohort of symptomatic Chinese patients with ARVD/C. N852fsX930 appeared to be a hot-spot mutation in which patients presented with a severe ARVD/C phenotype, and 2/3 had early onset of arrhythmic events. No significant difference was found in phenotype characteristics between patients with ARVD/C with and without PKP2 mutations. The decreased penetrance indicated that an ARVD/C diagnosis cannot solely rely on genotyping results.