MUTATIONS IN CARDIAC ION CHANNEL GENES IN KAZAKHSTANI PATIENTS WITH LONG QT SYNDROME

Abstract

Introduction. Cardiac arrhythmias are the most common among the group of cardiovascular diseases (CVD), and have a risk of sudden cardiac death (SCD). Long QT syndrome (LQTS) is a heritable disease characterized by prolongation of the QT interval on an electrocardiogram (ECG), which often leads to syncope and SCD. Currently, identification of mutations in cardiac ion channel genes in patients with LQTS and recognition of genetic causes of the syndrome are actual in cardiology. Aim. To identify cardiac ion channel mutations in genes associated with long QT syndrome in Kazakhstani patients. Materials and methods. This study was designed as a cohort study. At present, our study has identified three patients with LQTS. Nevertheless, the recruitment of additional patients with LQTS for the study is ongoing. Illumina TruSight Cardio panel was used for genetic screening. The cardiopanel consists of 174 genes associated with cardiac disorders including LQTS. After a targeted sequencing, data analysis was carried out using the programs SureCall version 2.0.7.0 (Agilent Technologies, Santa Clara, California, USA), ANNOVAR, GTK, bwa, bowtie, bow tie 2, VarScan, etc. Results. Clinically significant variants were found in patients with LQTS. Namely, in genes SCN5A (c.G5296A:p.E1766K) and KCNH2 (c.C662T:p.A221V). Both variants are pathogenic and cause CVDs, specifically LQTS. In addition, c.G3785A mutation (p.R1262Q), a variant of uncertain significance in SCN5A gene was detected in one patient. Although there is insufficient data to determine the role of the variant in development of the disease. Conclusions. Screening for mutations in cardiac ion channel genes in patients with LQTS revealed clinically significant mutations. This research will be useful for Kazakhstani patients with LQTS in evaluation of required genetic testing and reliable genetic guidance to prevent SCD and distinguish between various arrhythmias.