A Mutation in CALM1 Encoding Calmodulin in Familial Idiopathic Ventricular Fibrillation in Childhood and Adolescence.

Details

Serval ID
serval:BIB_BD99F0200585
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Mutation in CALM1 Encoding Calmodulin in Familial Idiopathic Ventricular Fibrillation in Childhood and Adolescence.
Journal
Journal of the American College of Cardiology
Author(s)
Marsman R.F., Barc J., Beekman L., Alders M., Dooijes D., van den Wijngaard A., Ratbi I., Sefiani A., Bhuiyan Z.A., Wilde A.A., Bezzina C.R.
ISSN
1558-3597 (Electronic)
ISSN-L
0735-1097
Publication state
Published
Issued date
2014
Volume
63
Number
3
Pages
259-266
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
21/02/2014 19:17
Last modification date
20/08/2019 16:31
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