title: RYR2 sequencing reveals novel missense mutations in a Kazakh idiopathic ventricular tachycardia study cohort.
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.
authors: Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
authors: Ainur
authors: A
authors: Akilzhanova
authors: Center of Medical Research, Medical University of Graz, Graz, Austria, Graz, Austria.
authors: Christian
authors: C
authors: Guelly
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Omirbek
authors: O
authors: Nuralinov
authors: Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
authors: Zhannur
authors: Z
authors: Nurkina
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Dinara
authors: D
authors: Nazhat
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Shalkhar
authors: S
authors: Smagulov
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Azat
authors: A
authors: Tursunbekov
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Anar
authors: A
authors: Alzhanova
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Gulzhaina
authors: G
authors: Rashbayeva
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Ayan
authors: A
authors: Abdrakhmanov
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Sholpan
authors: S
authors: Dosmagambet
authors: Center of Medical Research, Medical University of Graz, Graz, Austria, Graz, Austria.
authors: Slave
authors: S
authors: Trajanoski
authors: Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
authors: Zhaxybay
authors: Z
authors: Zhumadilov
authors: Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
authors: Almaz
authors: A
authors: Sharman
authors: National Scientific Cardiac Surgery Center, Astana, Republic of Kazakhstan.
authors: Mahabbat
authors: M
authors: Bekbosynova
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D015870:Gene Expression; D006801:Humans; D007623:Kazakhstan; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000503:physiopathology
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel