Whereas RYR2 gain-of-function mutations have been associated with CPVT, arrhythmogenic cardiomyopathies, and AF, loss-of-function mutations in RYR2 can cause an arrhythmia syndrome recently termed Ca2 + release deficiency syndrome (CRDS)261. This evidence concerns the gene RYR2 and catecholaminergic polymorphic ventricular tachycardia.