The genetics underlying idiopathic ventricular fibrillation : A special role for catecholaminergic polymorphic ventricular tachycardia?

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Leinonen , J T , Crotti , L , Djupsjobacka , A , Castelletti , S , Junna , N , Ghidoni , A , Tuiskula , A M , Spazzolini , C , Dagradi , F , Viitasalo , M , Kontula , K , Kotta , M-C , Widen , E , Swan , H & Schwartz , P J 2018 , ' The genetics underlying idiopathic ventricular fibrillation : A special role for catecholaminergic polymorphic ventricular tachycardia? ' , International Journal of Cardiology , vol. 250 , pp. 139-145 . https://doi.org/10.1016/j.ijcard.2017.10.016

Title: The genetics underlying idiopathic ventricular fibrillation : A special role for catecholaminergic polymorphic ventricular tachycardia?
Author: Leinonen, Jaakko T.; Crotti, Lia; Djupsjobacka, Aurora; Castelletti, Silvia; Junna, Nella; Ghidoni, Alice; Tuiskula, Annukka M.; Spazzolini, Carla; Dagradi, Federica; Viitasalo, Matti; Kontula, Kimmo; Kotta, Maria-Christina; Widen, Elisabeth; Swan, Heikki; Schwartz, Peter J.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Kardiologian yksikkö
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Kimmo Kontula Research Group
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
Date: 2018-01-01
Language: eng
Number of pages: 7
Belongs to series: International Journal of Cardiology
ISSN: 0167-5273
URI: http://hdl.handle.net/10138/298140
Abstract: Background: Ventricular fibrillation (VF) is a major cause of sudden cardiac death. In some cases clinical investigations fail to identify the underlying cause and the event is classified as idiopathic (IVF). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility, screening for disease-predisposing variants could improve IVF diagnostics. Methods and results: The study included 76 Finnish and Italian patients with a mean age of 31.2 years at the time of the VF event, collected between the years 1996-2016 and diagnosed with idiopathic, out-of-hospital VF. Using whole-exome sequencing (WES) and next-generation sequencing (NGS) approaches, we aimed to identify genetic variants potentially contributing to the life-threatening arrhythmias of these patients. Combining the results from the two study populations, we identified pathogenic or likely pathogenic variants residing in the RYR2, CACNA1C and DSP genes in 7 patients (9%). Most of them(5, 71%) were found in the RYR2 gene, associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). These genetic findings prompted clinical investigations leading to disease reclassification. Additionally, in 9 patients (11.8%) we detected 10 novel or extremely rare (MAF <0.005%) variants that were classified as of unknown significance (VUS). Conclusion: The results of our study suggest that a subset of patients originally diagnosed with IVF may carry clinically-relevant variants in genes associated with cardiac channelopathies and cardiomyopathies. Although misclassification of other cardiac channelopathies as IVF appears rare, our findings indicate that the possibility of CPVT as the underlying disease entity should be carefully evaluated in IVF patients. (C) 2017 Elsevier B.V. All rights reserved.
Subject: Idiopathic ventricular fibrillation
Genetics
Catecholaminergic polymorphic ventricular tachycardia
RYR2
Genetic testing
LONG-QT SYNDROME
CARDIAC-ARREST
SEQUENCE VARIANTS
HYPERTROPHIC CARDIOMYOPATHY
FOLLOW-UP
MUTATIONS
GUIDELINES
DISEASE
CHANNEL
ASSOCIATION
3121 General medicine, internal medicine and other clinical medicine
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