title: GJA1 gene variations in sudden unexplained nocturnal death syndrome in the Chinese Han population.
abstract: Sudden unexplained nocturnal death syndrome (SUNDS) is a conundrum to both forensic pathologists and physicians, more than 80% of which the molecular pathogenesis remains unclear. Reported studies on both clinical and genetic phenotypes suggest SUNDS is related to congenital and acquired arrhythmias. Recent researches have linked the mutations of gene gap junction alpha 1 (GJA1) with arrhythmogenic cardiac disorders. In the present study, we investigate the potential correlation between GJA1 gene variations and the occurrence of SUNDS. Genomic DNA was extracted from the blood samples of both 124 sporadic SUNDS patients and 125 healthy controls to screen GJA1 gene for candidate variants using polymerase chain reaction (PCR) and direct DNA sequencing. One novel homozygous variant c.169C>T and one heterozygous SNP c.624C>T (rs530633057) were determined in 124 SUNDS cases (one case for each detected variant) and none of the 125 healthy controls. Base C>T transition at nucleotide position 169 led to termination of protein production after glutamine (Q) at codon 57 which is very likely to result in decreased expression of Cx43 gap junction channels and cause arrhythmic sudden death. This is the first report of GJA1 gene variations in SUNDS in the Chinese Han population, which suggests a novel susceptibility gene for Chinese SUNDS.
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yeda
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Shuangbo
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: chengjd@mail.sysu.edu.cn.
authors.forename: Jianding
authors.initials: J
authors.lastname: Cheng
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D018031:Connexin 43 / Q000235:genetics*; D003645:Death, Sudden / Q000209:etiology*; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human
keywords: GJ channels; GJA1 gene; Sudden unexplained nocturnal death syndrome; Variant