RYR2 sequencing reveals novel missense mutations in a Kazakh Idiopathic ventricular tachycardia study cohort
Loading...
Date
2014
Authors
Akilzhanova, Ainur
Guelly, Christian
Nuralinov, Omirbek
Nurkina, Zhannur
Nazhat, Dinara
Smagulov, Shalkhar
Tursunbekov, Azat
Alzhanova, Anar
Rashbayeva, Gulzhaina
Abdrakhmanov, Ayan
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS ONE. doi:10.1371/journal.pone.0101059
Abstract
Channelopathies, caused by disturbed potassium or calcium ion management in cardiac myocytes are a major cause of heart failure and sudden cardiac death worldwide. The human ryanodine receptor 2 (RYR2) is one of the key players tightly regulating calcium efflux from the sarcoplasmic reticulum to the cytosol and found frequently mutated (,60%) in context of catecholaminergic polymorphic ventricular tachycardia (CPVT1). We tested 35 Kazakhstani patients with episodes of ventricular arrhythmia, two of those with classical CPVT characteristics and 33 patients with monomorphic idiopathic
ventricular arrhythmia, for variants in the hot-spot regions of the RYR2 gene. This approach revealed two novel variants; one de-novo RYR2 mutation (c13892A.T; p.D4631V) in a CPVT patient and a novel rare variant (c5428G.C; p.V1810L) of
uncertain significance in a patient with VT of idiopathic origin which we suggest represents a low-penetrance or susceptibility variant. In addition we identified a known variant previously associated with arrhythmogenic right ventricular
dysplasia type2 (ARVD2). Combining sets of prediction scores and reference databases appeared fundamental to predict the pathogenic potential of novel and rare missense variants in populations where genotype data are rare.
Description
Keywords
RYR2 sequencing, human ryanodine receptor, ventricular arrhythmia, Tachycardia
Citation
Akilzhanova A, Guelly C, Nuralinov O, Nurkina Z, Nazhat D, et al. (2014) RYR2 Sequencing Reveals Novel Missense Mutations in a Kazakh Idiopathic Ventricular Tachycardia Study Cohort. PLoS ONE 9(6): e101059. doi:10.1371/journal.pone.0101059