SCREENING OF hRYR2 MUTATIONS IN PATIENTS WITH VENTRICULAR TACHYCARDIA IN KAZAKHSTAN: TWO NOVEL POINT MUTATIONS
A. Akilzhanova, C. Gülly, Z. Nurkina, O. Nuralinov, B. Abdirova, S. Dosmagambet, Z. Zhumadilov, A. Sharman, M. Bekbosynova
Department of Genomic and Personalised Medicine, Center for Life Scienses, Nazarbayev University, Astana, Kazakhstan. Organization for Research Infrastructure Center for Medical Research, Medical University of Graz, Graz, Austria 3National Scientific Cardiosurgery Center, Astana, Kazakhstan
Introduction: Ventricular arrhythmias are the leading cause of morbidity and mortality worldwide, causing sudden cardiac deaths and making this a major public health concern.
Methods: We screened two patients with CPVT (OMIM: 604772, Ventricular tachycardia, catecholaminergic polymorphic) and 14 patients with ventricular tachycardia for genetic variants in the mutational hot-spot regions of the human ryanodine receptor gene 2 (hRYR2). The target regions of hRYR2 including the most relevant 45 exons (coding and intronic splice-site regions of the exons) were amplified by PCR and directly sequenced. This candidate gene approach revealed one novel mutation in a CPVT patient (c.A13892T; p.D4631V) and a novel mutation in one patient with VT (c.G5428C; p.V1810L). Both variants are located at phylogenetically conserved positions and predicted pathogenetic. Three known synonymous SNPs rs3765097, rs2253273 and TMP ESp1 237664067 were detected in the study group. No further variants within the target regions were detected in the study group.
Conclusions: The present study will be helpful in the evaluation of the need for genetic screening and reliable genetic counseling for Kazakhstan patients with arrhythmias for forecasting and prevention of sudden cardiac death.
