Identification Of Potential Candidate Genes In Atrioventricular Nodal Reentrant Tachycardia By Whole Exome Sequencing

BackgroundAtrioventricular nodal reentrant tachycardia(（Atrioventricular nodal reentrant Tachycardia,AVNRT）is one of the most common rapid supraventricular arrhythmias.Familial aggregation,early onset of symptoms and absence of cardiac structural abnormalities suggest that genetic factors may be involved in the pathophysiology of AVNRT.In recent years,with the rapid development of molecular genetics,more and more data show that gene mutations are involved in the pathogenesis and maintaince of AVNRT.At present,specific genes related to the pathogenesis of AVNRT have not been fully elucidated.Further genetic studies are needed to understand the genetic effects and pathophysiological mechanisms of AVNRT.ObjectiveTo explore the potential pathogenic genes in family with familial AVNRT cases.Methods（1）The medical record retrieval tool system was used to search the families of patients with positive family history diagnosed by PSVT in the Department of Cardiology of Puyang Oilfield General Hospital affiliated to Xinxiang Medical College from January2018 to January 2020;the case information was integrated and analyzed;according to the wishes of the patients,intracardiac electrophysiological examination and radiofrequency ablation were performed,and the patients diagnosed with AVNRT were enrolled into the group.The written informed consent for gene screening was obtained from all participants.this study was approved by the Ethics Committee of Puyang Oil Field General Hospital.2ml of peripheral blood samples of patients and their parents were taken and gene sequencing was carried out by Whole exome sequencing.Then the first generation sequencing should be used to detect the DNA of the proband’s parents to verify the mutation sites.（2）Reference genes,mutant genes,and the functional pathway were performed,A protein-protein interaction（PPI）network was then established;the WES data in the genetic studies of Danish AVNRT patients and Chinese AVNRT patients were used for external data validation.ResultsIn this study,Whole exome sequencing was performed in 1 family with AVNRT.3rare variants of 3 genes were identified in 69 reference genes（Minor allele frequency（MAF）< 0.001）.Gene-based pathway significance analysis revealed functional pathways related to AVNRT,including neurotransmitter release,cardiac ion channels.Considering the gene function and external data verification,the most likely candidate gene are LMNA,CACNA1 C,and TTN.ConclusionsThe preliminary results showed the possible potential candidate genes,such as LMNA,CACNA1 C and TTN;the pathways mediated by these genes,neurotransmitter release and cardiac ion channels might be involved in the pathogenesis and maintaince of AVNRT;As combined with reported data,the cumulative effect of multiple genes were not excluded.