Mutations of Desmoglein-2 in Sudden unexplained death in the chinese han population

Abstract

Sudden unexplained death (SUD) remains a puzzle in forensic medicine. Desmoglein-2 (DSG2) has been linked to arrhythmogenic right ventricular cardiomyopathy which may cause life-threatening ventricular arrhythmias and sudden death. Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy. We hypothesized that DSG2 mutations may be responsible for certain Chinese SUD cases. We sequenced all 15 exons of DSG2 in DNA extracted from postmortem heart tissues of 25 Chinese patients dying from SUD. The primers were designed using the Primer Express 3.0 software. Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130 Xl Genetic Analyzer. Mutation damage prediction was made using Mutation Taster, PolyPhen, and SIFT software. In 2 of 25 cases of Chinese SUD samples, two DSG2 heterozygous mutations (p.P927 L and p.T1070M) were identified, and one is probably damaging. We concluded that DSG2 mutations may be related to the occurrence of part of SUD cases in the Chinese Han population.

Keywords

• Desmoglein-2
• desmosomal mutation
• sudden cardiac death
• sudden unexplained death