Novel plakophilin2 mutation. Three generation family with arrhythmogenic right ventricular cardiomyopathy

• Objectives: The autosomal dominant form of arrhythmogenic right ventricular cardiomyopathy (ARVC)has been linked to mutations in desmosomal proteins. Different studies have shown that amutation in plakophilin-2 (PKP 2) is a frequent genetic cause for ARVC. We describe a newmutation in the PKP2 gene, the genotype-phenotype variation in this mutation and its clinicalconsequences. Design: Individuals in a three generation family were investigated after the sudden cardiac death of a young male. Clinical evaluation, electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy and genetic testing were performed. Results: A novel heterozygote mutation, a c.368G>A transition, located in exon 3 of the PKP2 gene was found (p.Trp123X). The phenotype was characterized by arrhythmia at an early age in some individuals, with mild abnormalities on imaging. However a relative carrying this mutation, with positive findings on endomyocardial biopsy had an otherwise normal phenotype, for 16 years, whereas a relative fulfilling the modified Task Force Criteria for ARVC turned out to be a non-carrier. Conclusions: This shows the variable penetrance and phenotypic expression in ARVC and highlights the need of genetic testing as well as a thorough phenotype examination as a part of the investigations in ARVC pedigrees.

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