title: Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population.
abstract: Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Clinical features of SUNDS survivors suggested that SUNDS is similar to Brugada syndrome (BrS). Leucine-rich repeat containing 10 (LRRC10) gene was a newly identified gene linked to dilated cardiomyopathy, a disease associated with sudden cardiac death. To investigate the prevalence and spectrum of genetic variants of LRRC10 gene in SUNDS and BrS, the coding regions of LRRC10 were genetically screened in 113 sporadic SUNDS victims (from January 2005 to December 2015, 30.7 ± 7.5 years) and ten BrS patients (during January 2010 to December 2014, 38.7 ± 10.3 years) using direct Sanger sequencing. Afterwards, LRRC10 missense variant carriers were screened for a panel of 80 genes known to be associated with inherited cardiac arrhythmia/cardiomyopathy using target-captured next-generation sequencing. In this study, an in silico-predicted malignant LRRC10 mutation p.E129K was detected in one SUNDS victim without pathogenic rare variant in a panel of 80 arrhythmia/cardiomyopathy-related genes. We also provided evidence to show that rare variant p.P69L might contribute to the genetic cause for one SUNDS victim and two BrS family members. This is the first report of genetic screening of LRRC10 in Chinese SUNDS victims and BrS patients. LRRC10 may be a new susceptible gene for SUNDS, and LRRC10 variant was initially and genetically linked to BrS-associated arrhythmia.
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shuangbo
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 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, Guangdong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yin
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 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, Guangdong, 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, Guangdong, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Makielski
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. chengjd@mail.sysu.edu.cn.
authors.forename: Jianding
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D053840:Brugada Syndrome / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003645:Death, Sudden / Q000209:etiology*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C000607442:LRRC10 protein, human; D008840:Microfilament Proteins
keywords: Forensic pathology; Genetics; Leucine-rich repeat containing 10 (LRRC10) gene; Sudden cardiac death