Arrhythmogenic Right Ventricular Cardiomyopathy Caused By Sudden Cardiac Death Relationship Between Genotype And Phenotype Of The Patient

Objective:Sudden cardiac death(SCD) is often the first symptom of arrhythmogenic right ventricular cardiomyopathy(ARVC). Therefore,the study in mechanism of SCD caused by ARVC is very important.To find the way of early diagnosis of the disease in order to reduce mortality has great clinical significant. In this study, genetic testing and clinical data analysis were carried out on patients with SCD triggered by ARVC, and disease-related mutations which lead to sudden death were screened.To analyze the Genotype-phenotype relationship in order to investigate the risk factors of SCD caused by ARVC from the perspective of molecular biology.Method:The coding exons and intronic regions of9disease-causing genes of15SCD patients caused by ARVC were captured and sequenced by next generation sequencing. Identified mutations in patients were confirmed by Sanger capillary sequencing. The9disease-causing genes are:DSP,DSG2,DSC2,PKP2,JUP,TGF-β3, TMEM43,DES and LMNA. Clinical data of patients was collected,including personal history, family history, echocardiography, ECG,etc, and the genotype-phenotype relationship in these patients was analyzed.Results:15mutations were identified in9SCD patients.13mutations were found in desmosomal genes, including PKP2(6),DSG2(3),DSP (2),JUP (2);2mutations were identified in non-desmosomal genes,including TMEM43(1),TGF β3(1).Mutations located on the PKP2gene have a large proportion (67%), including3(50%) truncated mutations. Multiple mutations carriers accounted for67%. All patients were under the age of60, and mutation carriers in patients had small differences with non-carriers in the age of SCD, family history, and structural abnormalities.Mutations carriers had an younger age of onset than non-carriers (P=0.032),and the proportion of males was significantly greater than mutations non-carriers (P=0.011); the proportion of mutation carriers those who had previous syncope history was larger than non-carriers (P=0.041); and the proportion of occurrence of ventricular tachycardia was significantly greater than non-carriers (P=0.011).Conclusion:(1)Mutations carriers has an earlier age of onset, and a higher proportion of critical symptoms in sudden death, so these identified mutations in this study may have relationship with SCD caused by ARVC;(2)Multiple mutations carriers had a larger proportion, so carrying multiple mutations may be a risk factor of SCD caused by ARVC;(3)Most of the mutations were found in desmosomal genes,and mutations in PKP2 gene had a larger proportion.