Identification of a novel TECRL variant causing type 3 catecholaminergic polymorphic ventricular tachycardia

Abstract

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a leading cause of sudden cardiac death (SCD) in young patients, characterized by bidirectional or polymorphic ventricular tachycardia often induced by physical exertion or emotional stress.

Results: We analyzed a 12-year-old girl with CPVT who suffered cardiac and respiratory arrest. Clinical data were derived from medical records. Whole-exome sequencing (WES) and Sanger sequencing identified two missense mutations in the trans-2,3-enoyl-CoA reductase-like (TECRL) gene (NM_001010874.5: c.587G > A p.Arg196Gln and NM_001010874.5: c.868C > T p.Pro290Ser), potentially pathogenic and associated with type 3 CPVT (CPVT3). Functional studies suggested both mutations could lead to reduced protein expression. We also discovered a novel TECRL mutation (NM_001010874.5: c.868C > T p.Pro290Ser). This study further supports the role of TECRL as one cause of CPVT.

Conclusions: In this study, functional studies implicate these variants as the cause of CPVT in this patient.

Keywords: TECRL; catecholaminergic polymorphic ventricular tachycardia; functional analysis; long QT syndrome; pediatric; sudden cardiac death.

Figure 1

The patient's electrocardiogram indicated arrhythmia. (A) The electrocardiogram suggested frequent ventricular premature beats, some occurring in pairs. (B) Prolonged QT interval:QT time = 0.53 s (QTc:0.65 s).

Figure 2

The mutation c.587G > A:p.Arg196Gln and c.868C > T:p.Pro290Ser affects TECRL expression. wt, wild type TECRL; m1/mut1: c.587G > A:p.Arg196Gln;m2/mut2: c.868C > T:p.Pro290Ser. (A) Sequencing results showed that mutation c.587G > A:p.Arg196Gln and c.868C > T:p.Pro290Ser were successfully introduced; (B) mRNA expression detected by qPCR; (C) TECRL protein expression results by WB; (D) Bar graph of gray-scale scan statistics of WB results; (E) Gel electrophoresis image of quantitative RT-PCR results.