A de novo heterozygous cardiac ryanodine receptor gene (RYR2) mutation in a catecholaminergic polymorphic ventricular tachycardia patient

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most common causes of sudden cardiac death (SCD) during childhood and adolescence. A de novo heterozygous Glu2296Lys mutation in the ryanodine receptor 2 (RyR2) was identified in a 5-year-old boy with CPVT by whole exome sequencing (WES), and it was confirmed by Sanger sequencing. No mutation was found in his healthy parents. Neural network analysis predicted that a Glu2296Lys mutation could decrease the stability of the RYR2 protein, with a confidence score of −0.8831. A STRUM server prediction also confirmed that a Glu2296Lys mutation could reduce RYR2 protein stability. Thus, we confirmed that the Glu2296Lys mutation may play a critical role in the stability of RYR2, which is associated with CPVT. So, the de novo RYR2 mutation may cause CPVT in this patient, but further evidence is needed to prove causality.