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A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence.
- Source :
-
Journal of the American College of Cardiology [J Am Coll Cardiol] 2014 Jan 28; Vol. 63 (3), pp. 259-66. Date of Electronic Publication: 2013 Sep 25. - Publication Year :
- 2014
-
Abstract
- Objectives: This study aimed to identify the genetic defect in a family with idiopathic ventricular fibrillation (IVF) manifesting in childhood and adolescence.<br />Background: Although sudden cardiac death in the young is rare, it frequently presents as the first clinical manifestation of an underlying inherited arrhythmia syndrome. Gene discovery for IVF is important as it enables the identification of individuals at risk, because except for arrhythmia, IVF does not manifest with identifiable clinical abnormalities.<br />Methods: Exome sequencing was carried out on 2 family members who were both successfully resuscitated from a cardiac arrest.<br />Results: We characterized a family presenting with a history of ventricular fibrillation (VF) and sudden death without electrocardiographic or echocardiographic abnormalities at rest. Two siblings died suddenly at the ages of 9 and 10 years, and another 2 were resuscitated from out-of-hospital cardiac arrest with documented VF at ages 10 and 16 years, respectively. Exome sequencing identified a missense mutation affecting a highly conserved residue (p.F90L) in the CALM1 gene encoding calmodulin. This mutation was also carried by 1 of the siblings who died suddenly, from whom DNA was available. The mutation was present in the mother and in another sibling, both asymptomatic but displaying a marginally prolonged QT interval during exercise.<br />Conclusions: We identified a mutation in CALM1 underlying IVF manifesting in childhood and adolescence. The causality of the mutation is supported by previous studies demonstrating that F90 mediates the direct interaction of CaM with target peptides. Our approach highlights the utility of exome sequencing in uncovering the genetic defect even in families with a small number of affected individuals.<br /> (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Child
DNA Mutational Analysis
Electrocardiography
Female
Humans
Male
Pedigree
Ventricular Fibrillation metabolism
Ventricular Fibrillation physiopathology
Calmodulin genetics
DNA genetics
Genetic Predisposition to Disease
Monomeric Clathrin Assembly Proteins genetics
Mutation
Ventricular Fibrillation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1558-3597
- Volume :
- 63
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American College of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 24076290
- Full Text :
- https://doi.org/10.1016/j.jacc.2013.07.091