1. The genetics underlying idiopathic ventricular fibrillation: A special role for catecholaminergic polymorphic ventricular tachycardia?
- Author
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Aurora Djupsjöbacka, Federica Dagradi, Maria Christina Kotta, Jaakko T. Leinonen, Elisabeth Widen, Alice Ghidoni, Annukka M. Tuiskula, Kimmo Kontula, Lia Crotti, Peter J. Schwartz, Nella Junna, Silvia Castelletti, Heikki Swan, Matti Viitasalo, Carla Spazzolini, Institute for Molecular Medicine Finland, University of Helsinki, Kardiologian yksikkö, HUS Heart and Lung Center, Kimmo Kontula Research Group, Clinicum, Department of Medicine, HUS Internal Medicine and Rehabilitation, Elisabeth Ingrid Maria Widen / Principal Investigator, Centre of Excellence in Complex Disease Genetics, Genomic Discoveries and Clinical Translation, Leinonen, J, Crotti, L, Djupsjöbacka, A, Castelletti, S, Junna, N, Ghidoni, A, Tuiskula, A, Spazzolini, C, Dagradi, F, Viitasalo, M, Kontula, K, Kotta, M, Widén, E, Swan, H, and Schwartz, P
- Subjects
Male ,0301 basic medicine ,Genetic testing ,RYR2 ,Disease ,030204 cardiovascular system & hematology ,GUIDELINES ,Ryanodine receptor 2 ,DISEASE ,Sudden cardiac death ,Cohort Studies ,0302 clinical medicine ,CHANNEL ,CARDIAC-ARREST ,SEQUENCE VARIANTS ,Idiopathic ventricular fibrillation ,Child ,Finland ,Likely pathogenic ,HYPERTROPHIC CARDIOMYOPATHY ,ASSOCIATION ,Middle Aged ,3. Good health ,Italy ,Idiopathic ventricular fibrillation, Genetics, Catecholaminergic polymorphic ventricular tachycardia, RYR2, Genetic testing ,Catecholaminergic polymorphic ventricular tachycardia ,Ventricular Fibrillation ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Adult ,medicine.medical_specialty ,Adolescent ,BIO/18 - GENETICA ,LONG-QT SYNDROME ,Young Adult ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Humans ,MUTATIONS ,business.industry ,Genetic Variation ,Mean age ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,Sequence Analysis, DNA ,medicine.disease ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Mutation ,Ventricular fibrillation ,Tachycardia, Ventricular ,FOLLOW-UP ,business - 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
- Published
- 2018
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