title: Mutations of desmoglein-2 in sudden death from arrhythmogenic right ventricular cardiomyopathy and sudden unexplained death.
abstract: Desmoglein-2 (DSG2), a member of the desmosomal cadherin superfamily, has been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC)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 sequenced all 15 exons of DSG2 in DNA extracted from post-mortem heart tissues of 25 patients dying with ARVC and 25 from sudden unexplained death (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. 2 DSG2 mutations (p. S1026Q fsX12, p. G678R)in two ARVC samples and 2 DSG2 mutations(p. E 896K, p. A858 V) in two SUD samples were identified, all the mutations were novel. We concluded that DSG2 mutations may not specific for ARVC and may be related to the fatal arrhythmic events even in patients with a morphological normal heart.
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zmc830921@gmail.com.
authors: Mingchang
authors: M
authors: Zhang
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Aimin
authors: A
authors: Xue
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Yiwen
authors: Y
authors: Shen
authors: The Department of Laboratory Medicine, National Institutes of Health, Bethesda, USA.
authors: Joao Bosco
authors: JB
authors: Oliveira
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China; Division of Forensic Medicine, Key Laboratory of Evidence Sciences, China University of Political Science and Law, Beijing, China; University of Maryland Medical Center, Baltimore, USA.
authors: Ling
authors: L
authors: Li
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Ziqin
authors: Z
authors: Zhao
authors: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai, China; University of Maryland Medical Center, Baltimore, USA.
authors: Allen
authors: A
authors: Burke
mesh_terms: D000293:Adolescent; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D003645:Death, Sudden / Q000209:etiology*; D051301:Desmoglein 2 / Q000235:genetics*; D005091:Exons; D005260:Female; D053803:Forensic Genetics; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D051301:Desmoglein 2
keywords: Arrhythmogenic right ventricular cardiomyopathy; Desmoglein-2; Desmosomal mutation; Sudden cardiac death; Sudden unexplained death