Whole exome sequencing detected the main contributor to Atrial Fibrillation in an Iranian family

Background and Aim: Atrial fibrillation (AF) is the most common cardiac arrhythmias worldwide which carries a poor prognosis. Previous documentations reported different genes mutations involving in AF etiology and this heterogeneity, leads to limited success in candidate genes screening. Emerging whole exome sequencing (WES) might help to better diagnosis of AF etiology. To this purpose, we studied the causes of the AF in an Iranian family with several affected individuals.Methods: In the present study, whole exome sequencing was applied for the family, i.e., referred to Rajaie Cardiovascular Medical and Research Center and has multiple AF patients, to determine the underlying cause of AF. The candidate variations were confirmed and segregated by PCR and Sanger sequencing.Results: The WES revealed a reported missense heterozygous mutation, c.A۱۶۷۳G (p.H۵۵۸R) in the SCN۵A gene which predicted as a pathogenic variant by the most bioinformatics tools such as SIFT, Polyphen-۲, and MutationTaster. Moreover, this mutation was segregated in two affected brothers as heterozygous form.Conclusion: Given that mutations in SCN۵A gene are considered as one of the most known causes of AF, the found mutation seems to be the most probably disease causing variant in patients of this family. Furthermore, our study indicates that using the WES is an informative approach to find the etiology of heterogeneous disorders like AF.