The Association Between The Desmosomal Protein Genes Mutations Of ARVC And Yunnan Unexplained Sudden Death

ObjectiveA total of 97 exons of the ARVC bridging protein genes DSP,DSG2,PKP2,DSC2 and JUP were screened for mutations in Yunnan unexplained sudden death cases,co-occurring cases,relatives of cases and controls,and health screening based on electrocardiography and echocardiography was performed to investigate the genetic characteristics of the study subjects’ families.The combined study results screened for high-risk populations,elucidated the relationship between Yunnan unexplained sudden death and mutations in ARVC bridging protein pathogenic genes from a molecular genetic perspective,validated the hypothesis of the etiology of sudden death in Yunnan,and provided a basis for the development of targeted prevention and control measures.MethodsCardiac cavity blood was collected from cases of Yunnan unexplained sudden death,and anticoagulated peripheral venous blood was collected from concurrent cases,relatives of cases and control population as study samples with informed consent.Mutations in 97 exons of the five ARVC bridging protein genes were detected using the Sanger double deoxygenated chain end termination method,and the amino acid changes caused by the detected mutations were analysed to determine the type of mutation.A health examination based on ECG and echocardiography was performed on concurrent cases,case relatives and controls,and the genetic lineage of case families was investigated to compare and analyse the heart health status between different populations for genetic analysis.ResultsFinally,11 cases of Yunnan unexplained sudden death,1 case of co-morbidity,128 relatives of the cases and 60 controls were selected for mutation testing.52 mutations in36 exons were detected in the Yunnan unexplained sudden death cases,co-morbidity cases and relatives of the cases carrying the DSP gene(21),DSG2 gene(10),PKP2gene(8),DSC2 gene(8)and JUP gene(5).Of the 52 mutant loci,6(11.54%)were carried by Yunnan unexplained sudden death cases alone,2(3.85%)by co-occurring cases,35(67.31%)by relatives of cases alone,5(9.62%)by co-occurring cases of Yunnan unexplained sudden death cases and relatives of cases,and 5(9.62%)by co-occurring cases of Yunnan unexplained sudden death cases and relatives of cases.cases and co-occurring cases(3.85%);and 2 cases in the three groups(3.85%).Relatives of Yunnan unexplained sudden death involved a total of 56 families in 6 ward counties(cities).One family in Heqing County shared the same mutation locus with 5individuals,with significant family aggregation;10 families in Xiangyun County carried the same mutation locus,with significant regional aggregation.There were 17 types of relatives of cases with abnormal ECG alterations and as many as 21 types of villagers in the sick village;12 types of relatives of cases with abnormal echocardiogram detection and as many as 15 types of villagers in the sick village.ConclusionYunnan unexplained sudden death,co-occurring cases and relatives of cases in Yunnan all had mutations in the ARVC bridging protein gene to varying degrees,with a mutation rate of 37.11% and significant mutation specificity in different populations.There were significant family and village clustering of mutations among sudden death cases,co-occurring cases,and relatives of cases in Yunnan.ARVC should be the main cause in some Yunnan unexplained sudden death cases,with relatives of cases at higher risk of developing ARVC。...