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PLoS One. 2014 Jun 30;9(6):e101059. doi: 10.1371/journal.pone.0101059. eCollection 2014.

RYR2 sequencing reveals novel missense mutations in a Kazakh idiopathic ventricular tachycardia study cohort.

Author information

1
Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
2
Center of Medical Research, Medical University of Graz, Graz, Austria, Graz, Austria.
3
National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.

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.

PMID:
24978818
PMCID:
PMC4076244
DOI:
10.1371/journal.pone.0101059
[Indexed for MEDLINE]
Free PMC Article

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