Molecular Analysis of KCNQ1, KCNH2 and SCN5A Genes in Iranian Patients with Long QT Syndrome

Abstract

Background: Long QT syndrome is a cardiac ion channelopathy characterized by corrected QT interval prolongation on electrocardiograms, leading to syncope and sudden death. Methods: In this study, the genetic screening of four Iranian LQTS families, including two Romano Ward syndrome families and two families with Jervell and Lange‐Nielsen syndrome, was performed by Sanger sequencing and haplotype analysis for three of the most common LQTS genes, KCNQ1, KCNH2 and SCN5A. Results: A de novo mutation c.1838C>T in the KCNH2 gene associated with LQTS2 was identified in a RWS family. A homozygous mutation c.477+5G>A was found in the KCNQ1 of the two JLNS families, and a novel recessive KCNQ1 variant c.934A>T (p.T312S) was identified in the KCNQ1 of another RWS family. The structural, functional and pathogenicity evaluation of the novel KCNQ1 missense variant by in silico predictive programs along with the segregation and population studies revealed that the variant was a likely pathogenic mutation. Conclusion: To the best of our knowledge, p.T312S is the first mutation identified for an AR-RWS family in the Iranian families. This assay can be used to screen individuals to provide useful information for the identification of the LQTS in the Iranian population. It is yet to be proven that the detection of different types of LQT will result in a more effective therapy.