Functional Analysis of a Novel Heterozygous Variant in CASQ2 as a Distinct Cause of Catecholaminergic Polymorphic Ventricular Tachycardia

Variants in RYR2 and CASQ2 cause catecholaminergic polymorphic ventricular tachycardia (CPVT) 1 and 2, respectively. Most cases of CPVT2 are homozygous for CASQ2 variants. We recently reported the first large family with CPVT caused by a heterozygous CASQ2 variant. Here, we assess the functional mechanisms of this pathogenic CASQ2 variant and compare it to a CPVT1 (RYR2 variant) phenotype using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM).