Analysis of mutations in ARVC desmosomal protein gene in relatives of Yunnan unexplained sudden death cases in Nanjian County, Dali Prefecture / 中华地方病学杂志

ABSTRACT

Objective:To analyze the mutations in desmosomal protein genes of arrhythmogenic right ventricular cardiomyopathy (ARVC) in relatives of Yunnan unexplained sudden death (YUSD) cases in Nanjian County, Dali Prefecture, Yunnan Province, and provide a basis for etiological hypothesis and control measures.Methods:The blood samples of YUSD case relatives ( n = 7) and control villagers ( n = 7) were collected, and basic situation investigation and electrocardiography (ECG) examination were performed at the same time. Blood DNA was extracted as a template for PCR amplification, and Sanger method was used to perform plakophilin 2 (PKP2), desmoglein 2 (DSG2), desmocollin 2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) five ARVC desmosomal protein genes sequencing of a total of 97 exons, and comprehensive analysis of gene mutations was carried out. Results:Five of YUSD case relatives carried genetic mutation sites, including DSP gene heterozygous synonymous mutations about exon 20 c.2862 C>T (p.Cys954Cys) and exon 24F c.7122 C>T (p.Thr2374Thr), DSC2 gene heterozygous missense mutation about exon 15 c.2326 A>G (p.Ile776Val), and all the five people were single heterozygous mutation carriers. Among them, two case relatives of the father-son carried the same site mutation of the DSC2 gene; the abnormal ECGs of three YUSD case relatives were ST-T change or clockwise rotation. However, the mutation sites of PKP2, DSG2, DSC2, DSP and JUP genes in control villagers were not detected.Conclusions:YUSD case relatives in Nanjian County carry ARVC desmosomal protein genes DSP and DSC2 mutations. Pathogenic mutation of DSC2 gene c.2326 A>G (p.Ile776Val) is may related to the incidence of some YUSD cases.