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Nat Commun. 2016 Apr 12;7:11303. doi: 10.1038/ncomms11303.

A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation.

Author information

1
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada M5G 2C4.
2
Department of Medicine, Cardiovascular Research Institute and Division of Cardiology, University of California San Francisco, San Francisco, California 94158, USA.
3
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA.
4
Division of Cardiology, University Hospital, Western University, London, Ontario, Canada N6G 2V4.
5
Division of Cardiology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada M5G 2C4.
6
Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
7
Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada M5G 2C4.

Abstract

Atrial fibrillation (AF), the most common arrhythmia, is a growing epidemic with substantial morbidity and economic burden. Mechanisms underlying vulnerability to AF remain poorly understood, which contributes to the current lack of highly effective therapies. Recognizing mechanistic subtypes of AF may guide an individualized approach to patient management. Here, we describe a family with a previously unreported syndrome characterized by early-onset AF (age <35 years), conduction disease and signs of a primary atrial myopathy. Phenotypic penetrance was complete in all mutation carriers, although complete disease expressivity appears to be age-dependent. We show that this syndrome is caused by a novel, heterozygous p.Glu11Lys mutation in the atrial-specific myosin light chain gene MYL4. In zebrafish, mutant MYL4 leads to disruption of sarcomeric structure, atrial enlargement and electrical abnormalities associated with human AF. These findings describe the cause of a rare subtype of AF due to a primary, atrial-specific sarcomeric defect.

PMID:
27066836
PMCID:
PMC4832069
DOI:
10.1038/ncomms11303
[Indexed for MEDLINE]
Free PMC Article

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