RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling

Abstract

We show that loss of Rbm20 disturbs Ca²⁺ handling and leads to more proarrhythmic Ca²⁺ releases from the sarcoplasmic reticulum. Patients that carry a pathogenic RBM20 mutation have more ventricular arrhythmias despite a similar left ventricular function, in comparison with patients with a TTN mutation. Our experimental data suggest that RBM20 mutation carriers may benefit from treatment with an I_Ca,L blocker to reduce their arrhythmia burden.