Abstract 17663: One Mutation Fits All: Phospholamban R14del Causes Both Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Introduction: Comprehensive screening of genes encoding desmosomal proteins identifies a mutation in 40%-60% of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. Although considered separate entities, ARVC/D and dilated cardiomyopathy (DCM) show considerable clinical overlap. Therefore, we searched for genes that, when mutated, lead to DCM with an arrhythmogenic phenotype, which could potentially also solve genetically unexplained ARVC/D cases. We assessed the hypothesis that mutations in phospholamban (PLN) - important in Ca2+ homeostasis - are a cause of both DCM and ARVC/D.
Methods: We screened 163 DCM index-patients and 95 ARVC/D index-patients (fulfilling the 2010 taskforce criteria) for mutations in PLN and evaluated clinical characteristics.
Results: We identified the previously described PLN mutation R14del in 23 of 163 (14.1%) DCM index-patients and 10 of 95 (10.5%) ARVC/D index-patients (all desmosomal-mutation negative). Haplotype analysis revealed a common founder for all patients. The clinical characteristics and follow-up of index-patients carrying the PLN R14del mutation, compared to patients without a PLN mutation, are presented in Table 1.
Conclusions: The previously described PLN R14del mutation: 1. underlies a substantial part of Dutch ARVC/D cases; and 2. leads to a malignant form of DCM with a high rate of appropriate ICD interventions, sudden death in family members and HTx. These findings contribute to the elucidation of the pathophysiology of ARVC/D and arrhythmogenic forms of DCM. Table 1. Clinical characteristics of ARVC/D and DCM probands.
- © 2010 by American Heart Association, Inc.