Regional Variation in RBM20 Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy

摘要: Background Variants in the cardiomyocyte-specific RNA splicing factor RBM20 have been linked to familial cardiomyopathy, but causative genetic architecture and clinical consequences of this disease are incompletely defined. Methods Results To define we first established a database variants associated with cardiomyopathy compared these observed general population respect their location coding transcript. We identified 2 regions significantly enriched for cardiomyopathy-associated exons 9 11. then assembled registry 74 patients from 8 institutions across world (44 index cases 30 cascade testing). This patient revealed highly prevalent family history sudden cardiac death (51%) (72%) among high prevalence composite arrhythmias (including atrial fibrillation, nonsustained ventricular tachycardia, implantable defibrillator discharge, arrest, 43%). Patients harboring cardiomyopathy-enriched by our variant analysis were findings. Further, characteristics more than large cohorts dilated TTNtv not different cohort LMNA-associated cardiomyopathy. Conclusions Our data establish as penetrant arrhythmogenic These findings underline importance arrhythmia surveillance screening represent step defining causality on level.