Identification of two variants in and genes in a patient with catecholaminergic polymorphic ventricular tachycardia suggesting new candidate disease genes and digenic inheritance.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic syndrome characterized by life-threatening arrhythmias, a normal resting electrocardiogram and the absence of overt structural heart abnormalities. Mutations in  gene account for the large part of CPVT cases. Less frequently, mutations in  gene have been linked to the recessive form of the disease. Overall, approximately 35% of CPVT patients remain without a genetic etiology implying that other genes might be found causative of the disease. Here, we present a 6-year-old boy born to first-degree related parents, with a typical phenotype of CPVT and a family history of sudden cardiac death of his brother at 7 years. A trio-based whole exome sequencing was performed, and we identified a homozygous variant in gene and a heterozygous variant in gene. We hypothesized that the presence of the homozygous variant in accounts for the CPVT phenotype in this family and the heterozygous variant in gene may act as a modifier gene. Further studies are needed to determine the role of these genes in CPVT.