Genealogy and clinical course of catecholaminergic polymorphic ventricular tachycardia caused by the ryanodine receptor type 2 P2328S mutation
| Autor: | Elisabeth Widen, Mikael Koponen, Matti Viitasalo, Heikki Swan, Jaakko T. Leinonen, Terhi Nallinmaa-Luoto, Annukka M. Tuiskula, Lauri Toivonen, Kimmo Kontula, Annukka Marjamaa |
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| Přispěvatelé: | Department of Medicine, HUS Heart and Lung Center, Helsinki University Hospital Area, HUSLAB, Staff Services, Kimmo Kontula Research Group, University of Helsinki, Kardiologian yksikkö, Genomics of Sex Differences, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, HUS Internal Medicine and Rehabilitation, Clinicum |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Heredity Medical Implants Polymers Epidemiology Gene Identification and Analysis CHILDREN 030204 cardiovascular system & hematology Ryanodine receptor 2 THERAPY Sudden cardiac death 0302 clinical medicine Heart Rate Risk Factors Tachycardia Medicine and Health Sciences 030212 general & internal medicine MOLECULAR CHARACTERIZATION Polyvinyl Chloride Materials Multidisciplinary Hazard ratio ASSOCIATION Middle Aged 3. Good health Pedigree Chemistry Macromolecules Mutation (genetic algorithm) Physical Sciences Cardiology Population study Medicine Engineering and Technology Female FLECAINIDE medicine.drug Research Article Biotechnology Adult medicine.medical_specialty Adolescent Science Materials Science Bioengineering Catecholaminergic polymorphic ventricular tachycardia Syncope EVENTS 03 medical and health sciences Young Adult Signs and Symptoms Internal medicine medicine Genetics Humans Flecainide Mutation Detection ARRHYTHMIAS Proportional hazards model business.industry BETA-BLOCKERS Biology and Life Sciences Ryanodine Receptor Calcium Release Channel medicine.disease Polymer Chemistry GENE Haplotypes Medical Risk Factors 3121 General medicine internal medicine and other clinical medicine Mutation Tachycardia Ventricular Medical Devices and Equipment Clinical Medicine business SUDDEN CARDIAC DEATH |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 12, p e0243649 (2020) |
| Popis: | Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD). Aims We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation. Methods The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study. Kaplan-Meier graphs, log-rank test and Cox regression model were used to evaluate the clinical course. Results Genealogical study revealed a common ancestor couple living in the late 17th century. A total of 1837 living descendants were tested for RYR2 P2328S mutation unveiling 62 mutation carriers aged mean 39±23 years old. No arrhythmic deaths were documented among genotyped subjects, but 11 SCDs were detected in non-genotyped family members since 1970. Three genotyped patients (5%) suffered an aborted cardiac arrest (ACA), and 15 (25%) had a syncope triggered by exercise or stress. Rate of cardiac events was higher among patients who in exercise stress test showed a maximum rate of premature ventricular contractions >30/min (68% vs 17%, p Conclusions Previously undiagnosed CPVT patients may be identified by well-conducted genealogical studies. The RYR2 P2328S mutation causes a potentially severe phenotype, but its expression is variable, thus calling for additional studies on modifying factors. |
| Databáze: | OpenAIRE |
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