A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most common causes of sudden cardiac death (SCD) during childhood and in adolescence. Trans-2, 3-enoyl-CoA reductase-like (Tecrl) gene mutations (Arg196Gln and c.331+1G > A splice site mutation) were first reported in CPVT. Tecrl homozygous c.331+1G > A splice site mutation in iPSCs revealed a definite correlation between Tecrl and Ca2+ transport in cardiomyocytes. However, no other researchers have confirmed Tecrl mutations in CPVT with literature review. In this study, a case of compound heterozygosity in the Tecrl gene (Arg196Gln and c.918+3T > G splice site mutation) was first identified in a 13-year-old boy with CPVT by whole-exome sequencing (WES) and confirmed by Sanger sequence. Support vector machine and neural network analysis predicted that Arg196Gln mutation could decrease the stability of Tecrl structure, the confidence scores were -0.8929 and -0.9930. A STRUM server also confirmed that Arg196Gln mutation may decrease the binding capacity of the substrate and cause an amino acid substitution immediately upstream of the 3-oxo-5-alpha steroid 4-dehydrogenase domain. According to the "human splicing finder" indication and Alamut Visual Splicing Prediction, the c.918 + 3T > G mutation could influence Tecrl variable splicing. Thus, we confirmed that Tecrl as a new gene which is associated with CPVT.