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

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...

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Autores principales: Orr, Nathan, Arnaout, Rima, Gula, Lorne J., Spears, Danna A., Leong-Sit, Peter, Li, Qiuju, Tarhuni, Wadea, Reischauer, Sven, Chauhan, Vijay S., Borkovich, Matthew, Uppal, Shaheen, Adler, Arnon, Coughlin, Shaun R., Stainier, Didier Y. R., Gollob, Michael H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832069/
https://www.ncbi.nlm.nih.gov/pubmed/27066836
http://dx.doi.org/10.1038/ncomms11303
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author Orr, Nathan
Arnaout, Rima
Gula, Lorne J.
Spears, Danna A.
Leong-Sit, Peter
Li, Qiuju
Tarhuni, Wadea
Reischauer, Sven
Chauhan, Vijay S.
Borkovich, Matthew
Uppal, Shaheen
Adler, Arnon
Coughlin, Shaun R.
Stainier, Didier Y. R.
Gollob, Michael H.
author_facet Orr, Nathan
Arnaout, Rima
Gula, Lorne J.
Spears, Danna A.
Leong-Sit, Peter
Li, Qiuju
Tarhuni, Wadea
Reischauer, Sven
Chauhan, Vijay S.
Borkovich, Matthew
Uppal, Shaheen
Adler, Arnon
Coughlin, Shaun R.
Stainier, Didier Y. R.
Gollob, Michael H.
author_sort Orr, Nathan
collection PubMed
description 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.
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spelling pubmed-48320692016-04-25 A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation Orr, Nathan Arnaout, Rima Gula, Lorne J. Spears, Danna A. Leong-Sit, Peter Li, Qiuju Tarhuni, Wadea Reischauer, Sven Chauhan, Vijay S. Borkovich, Matthew Uppal, Shaheen Adler, Arnon Coughlin, Shaun R. Stainier, Didier Y. R. Gollob, Michael H. Nat Commun Article 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. Nature Publishing Group 2016-04-12 /pmc/articles/PMC4832069/ /pubmed/27066836 http://dx.doi.org/10.1038/ncomms11303 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Orr, Nathan
Arnaout, Rima
Gula, Lorne J.
Spears, Danna A.
Leong-Sit, Peter
Li, Qiuju
Tarhuni, Wadea
Reischauer, Sven
Chauhan, Vijay S.
Borkovich, Matthew
Uppal, Shaheen
Adler, Arnon
Coughlin, Shaun R.
Stainier, Didier Y. R.
Gollob, Michael H.
A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title_full A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title_fullStr A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title_full_unstemmed A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title_short A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
title_sort mutation in the atrial-specific myosin light chain gene (myl4) causes familial atrial fibrillation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832069/
https://www.ncbi.nlm.nih.gov/pubmed/27066836
http://dx.doi.org/10.1038/ncomms11303
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