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

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Date: April-June 2019
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 2,847 words
Lexile Measure: 1630L

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Byline: Junyi. Lin, Yulei. Yang, Ziqin. Zhao, Yiwen. Shen, Kaijun. Ma, Mingchang. Zhang

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.


Cases of sudden death in children and adults where no cause of death is found at autopsy may demonstrate morphologically normal myocardium. In this study, we used the term 'sudden unexplained death (SUD)' while recognizing that it is a heterogeneous group of disorders and does not define a specific syndrome. SUD accounts for up to 30% of sudden death in adults, while the etiology of SUD remains unclear. Recently, SUD has been linked to ion-channel mutations in up to 25% of cases, indicating that some deaths from SUD are due to channelopathies.[1]

Normal heart function relies on correct electric and metabolic coupling between myocardial cells, which is accomplished by intercalated disc (ID), comprising desmosomes, gap junctions, and adherens junctions.[2] Desmosomes are intercellular adhesive complex formed by five major components, including desmoglein (DSG), desmocollin (DSC), plakophilins (PKP), plakoglobin (PG), and desmoplakin (DSP). Recently, mutations in desmosomal genes have been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC),[3],[4],[5],[6],[7],[8],[9] which may cause life-threatening ventricular arrhythmias and sudden death.[10],[11]

In previous studies, we tested the plakophilin-2 (PKP2) and desmoglein-2 (DSG2) mutations, with heart tissue from patients dying of SUD in the Western population; 24% of SUD patients had PKP2 mutations[12] and 8% of SUD patients had DSG2 mutations,[13] which suggests that PKP2 and DSG2 mutations may result in SUD in the Western population. The goal of this current study was to evaluate the mutations in DSG2 from patients dying of SUD in the Chinese Han population.

Materials and Methods

Study subjects

Twenty-five cases dying from SUD were studied from the Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University [Table 1]. The study has been approved by the Ethics Committee of Fudan University, and the international ethical guidelines have been followed during this study. All cases were seen in consultation with a cardiovascular pathologist and a forensic pathologist and examined in a similar fashion.{Table 1}

Genotyping and sequence alignment...

Source Citation

Source Citation   

Gale Document Number: GALE|A592117542