Identification of Arrhythmia-Associated Gene Mutations in Chinese Patients with Primary Electrical Disorders or Sudden Cardiac Death

Abstract

Background: Sudden cardiac death (SCD), unexpected death based on sudden cardiac ejection cessation, accounts for 15–20% of unnatural deaths in developed countries. Primary electrical disorders (PEDs), a group of cardiac rhythm abnormalities without detectable structural heart disease, are a major cause of SCD in people younger than 35 years of age. Cardiac muscle contraction and relaxation are triggered by the action potential (AP), which is generated by ionic changes across the cell membrane. Thus, PEDs are influenced by mutations in AP-associated genes, such as KCNE1 and RYR2. Methods: We recruited six patients with SCD and 42 patients with arrhythmia with onset under the age of 25, and used targeted sequencing to determine the genetic etiologies. Results: We identified five mutations (RYR2: c.12269C>T, p.P4090L; KCNE1: c.169T>C, p.F57L; KCNQ1: c.853A>C, p.K285Q; KCNH2: c.793T>C, p.C265R, and TRPM4: c.2985_3012del, p.E996Gfs*118) in five families with PED/SCD. Conclusions: We detected five mutations and expanded the mutation spectrum of PED-associated genes, thus contributing to the clinical diagnosis of PED.