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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence
Journal of the American College of Cardiology, Volume 63, No. 3, Year 2014
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Description
Objectives This study aimed to identify the genetic defect in a family with idiopathic ventricular fibrillation (IVF) manifesting in childhood and adolescence. 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. Methods Exome sequencing was carried out on 2 family members who were both successfully resuscitated from a cardiac arrest. 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. 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. © 2014 by the American College of Cardiology Foundation.
Authors & Co-Authors
Marsman, Roos F.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Barc, Julien
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Netherlands, Amsterdam
Royal Netherlands Academy of Arts and Sciences - Knaw
Beekman, Leander
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Alders, Mariëlle
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Dooijes, Dennis
Netherlands, Utrecht
University Medical Center Utrecht
Van Den Wijngaard, Arthur
Netherlands, Maastricht
Carim School for Cardiovascular Disease
Ratbi, Ilham
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Sefiani, Abdelaziz
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Bhuiyan, Zahurul Alam
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Wilde, Arthur A.M.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Saudi Arabia, Jeddah
King Abdulaziz University
Bezzina, Connie Rose
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Statistics
Citations: 163
Authors: 11
Affiliations: 7
Identifiers
Doi:
10.1016/j.jacc.2013.07.091
ISSN:
07351097
e-ISSN:
15583597
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases