Young and early‐onset dilated cardiomyopathy with malignant ventricular arrhythmia and sudden cardiac death induced by the heterozygous LDB3, MYH6, and SYNE1 missense mutations

作者：Ting Zhao, Yuting Ma, Z. Zhang, Jianzhong Xian, Xiaojing Geng, Feng Wang, Jiana Huang, Zhe Yang, Yi Luo, Yubi Lin · 发表于：Annals of Noninvasive Electrocardiology · 年份：2021 · DOI：10.1111/anec.12840 · 被引用次数：36 · 研究领域：Cardiac electrophysiology and arrhythmias、Cardiomyopathy and Myosin Studies、Cardiovascular Effects of Exercise

BACKGROUND: The whole exome sequencing (WES) with targeted gene analysis is an effective diagnostic tool for cardiomyopathy. The early-onset sudden cardiac death (SCD) was commonly associated with dilated cardiomyopathy (DCM) induced by pathogenic genetic mutations. METHODS: In a Chinese Han family, the patient of 24 years old occurred with early-onset and DCM and died of SCD associated with ICD storms induced by repetitive ventricular tachycardia/fibrillation (VT/F). Genomic DNA samples of peripheral blood were conducted for WES and Sanger sequence. Then, we performed bioinformatics analysis for 200 genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations affecting the secondary structure, hydrophobicity, and phosphorylation of amino acids, protein properties, and their joint pathogenicity by ProtParam, SOPMA, and ORVAL algorisms. The protein-protein interaction was analyzed by STRING algorism. RESULTS: The mutations of LDB3 p.M456R, MYH6 p.S180Y, and SYNE1 p.S4607F were identified as "Damaging/Deleterious." The SYNE1 (p.S4607F) increased one of alpha helix and decreased one of beta sheet. The LDB3 (p.M456R) reduced one of beta sheet and increased one of beta turn. The MYH6 (p.S180Y) decreased two of beta sheets and four of beta turns, but significantly increased twelve coils. The hydrophobicity of amino acid residues and their adjacent sequences were decreased by LDB3 (p.M456R) and MYH6 (p.S180Y), and significantly i...