Novel Biallelic TECRL Gene Variants Associated with Familial Catecholaminergic Polymorphic Ventricular Tachycardia in A Chinese Family with A History of Sudden Cardiac Death.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmia syndrome often caused by biallelic variants in the TECRL gene. This study reviews a Chinese family with two generations and six members affected by CPVT. The proband experienced syncope, loss of consciousness after exercise, and recurrent seizures, with electrocardiograph showing prolonged QTc interval and extreme ventricular tachycardia. Her elder sister died of syncope and cardiac arrest after exercise. Genetic analysis identified compound heterozygous variants in the TECRL gene: c.587G>A (p.Arg196Gln) and c.868C>T (p.Pro290Ser), inherited from each parent. Other family members without symptoms only carried one heterozygous variant. The p.Arg196Gln variant was previously reported, but p.Pro290Ser was a novel variant. Molecular dynamics simulations and Western blot analysis suggested that the structural stability and expression levels of the mutant protein were altered. This study underscores the significance of molecular diagnostics in patients experiencing syncope or cardiac arrest triggered by environmental changes or exercise, as early detection can facilitate personalized care and targeted treatment.