Compound and heterozygous mutations of KCNQ1 in long QT syndrome with familial history of unexplained sudden death: Identified by analysis of whole exome sequencing and predisposing genes

Abstract

Introduction Long QT syndrome (LQTS) increases the risk of life‐threatening arrhythmia in young individuals with structurally normal hearts. Sixteen genes such as the KCNQ1, KCNH2, and SCN5A have been reported for association with LQTS. Case presentation We identified the compound heterozygous mutations in the KCNQ1 gene at c. G527A (p.W176X) and c.G1765A (p.G589S) predicted as “damaging.” The in‐silico analysis showed that when compared to the characteristics of mRNA and protein of wild‐type KCNQ1, the mRNA of c.G527A mutation was significantly different in the centroid secondary structure. The subunit coded by W176X would lose the transmembrane domains S3–S6 and helices A‐D. The protein secondary structure of G589S was slightly shortened in helix structure; the protein physics‐chemical parameters of W176X and G589S significantly and slightly changed, respectively. Conclusions The compound heterozygous mutations of W176X and G589S coexisting in KCNQ1 gene of homologous chromosomes, resulting in more severe phenotype, are the likely pathogenic and genetic risks of LQTS and USD in this Chinese family.

Open Access for the Annals of Noninvasive Electrocardiology

“…Other interesting papers include very up‐to‐date review on ECG characteristics in patients with heart failure and normal ejection fraction from UK (Nikolaidou et al, ) and comprehensive review paper on heart rate variability during endurance exercise from Germany (Gronwald & Hoos, ). Original papers worth attention include study on the association between metabolic syndrome and QRT angle from the United States, (Delhey, Jin, Thapa, & Delongchamp, ) paper on the association between morphology of left descendent coronary artery and ECG in ST‐elevation myocardial infarction from Japan (Fujii, Hasegawa, Nakamura, & Ikari, ), study on temporal changes of noninvasive electrocardiographic risk factors for sudden cardiac death (Xenogiannis et al ), and a paper on compound and heterozygous KCNQ1 mutations in LQTS from China ( Lin et al ).…”