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Journal articles
Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy.: MEPPC: a new SCN5A-related cardiac channelopathy
Gabriel Laurent
1, *
Samuel Saal
2
Mohamed Yassine Amarouch
3
Delphine Béziau
3
Roos Marsman
4
Laurence Faivre
2
Julien Barc
3
Christian Dina
3
Geraldine Bertaux
1
Olivier Barthez
1
Christel Thauvin-Robinet
2, 4
Philippe Charron
5
Véronique Fressart
6
Alice Maltret
7
Elisabeth Villain
7
Estelle Baron
3
Jean Mérot
3
Rodolphe Turpault
8
Yves Coudière
8
Flavien Charpentier
3
Jean-Jacques Schott
3
Gildas Loussouarn
3
Arthur Wilde
4
Jean-Eric Wolf
1
Isabelle Baró
3
Florence Kyndt
3
Vincent Probst
3
*
Corresponding author
Gabriel Laurent 1
Correspondent author
Samuel Saal 2
Author
Mohamed Yassine Amarouch 3
Author
Delphine M. Béziau 3
Author
Geraldine Bertaux 1
Author
Olivier Barthez 1
Author
Christel Thauvin-Robinet 2, 4
Author
Philippe Charron 5
Author
Véronique Fressart 6
Author
Alice Maltret 7
Author
Elisabeth Villain 7
Author
Estelle Baron 3
Author
Jean Mérot 3
Author IdHAL : jean-merot ORCID : https://orcid.org/0000-0003-1840-8728
Rodolphe Turpault 8
Author IdHAL : rodolphe-turpault
Yves Coudière 8
Author IdHAL : yves-coudiere ORCID : https://orcid.org/0000-0003-2687-3232
Flavien Charpentier 3
Author
Jean-Jacques Schott 3
Author IdHAL : jean-jacques-schott ORCID : https://orcid.org/0000-0002-9578-9475
Gildas Loussouarn 3
Author IdHAL : gildas-loussouarn ORCID : https://orcid.org/0000-0001-8007-5931
Arthur A. M. Wilde 4
Author
Jean-Eric Wolf 1
Author
Isabelle Baró 3
Author IdHAL : isabelle-baro ResearcherId : http://www.researcherid.com/rid/D-3604-2015 ORCID : https://orcid.org/0000-0003-4850-4171
Florence Kyndt 3
Author
Vincent Probst 3
Author
1
Service de Cardiologie [CHU de Dijon] (CHU Dijon - 14 rue Paul Gaffarel - 21079 Dijon - France)
- CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon - 14 rue Paul Gaffarel - 21079 Dijon - France)
2
Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) (CHU de Dijon - 14 rue Paul Gaffarel - BP 77908 - 21079 DIJON Cedex - France)
- CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon - 14 rue Paul Gaffarel - 21079 Dijon - France)
3
ITX - unité de recherche de l'institut du thorax UMR1087 UMR6291 (8 quai Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1087 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR6291 (France)
4
Department of Experimental Cardiology (Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam - Netherlands)
- Heart Failure Research Center (HFRC) (France)
- AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (Meibergdreef 9 1105 AZ Amsterdam - Netherlands)
- UvA - University of Amsterdam [Amsterdam] (Spui 21 1012 WX Amsterdam - Netherlands)
5
Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires (France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U956 (101, rue de Tolbiac, 75013 Paris - France)
6
Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire (6,10 Batiment La Peyronie, 83 Bd de l'Hôpital 75651 Paris Cedex 13 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
7
Service de cardiologie pédiatrique [CHU Necker] (CHU Necker Enfants Malades, 149 rue de Sèvres 75015 PARIS - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Necker - Enfants Malades [AP-HP] (149 Rue de Sèvres 75015 Paris - France)
8
LMJL - Laboratoire de Mathématiques Jean Leray (France)
- CNRS - Centre National de la Recherche Scientifique : UMR6629 (France)
- UN UFR ST - Université de Nantes - UFR des Sciences et des Techniques (2, rue de la Houssinière - BP 92208 - 44322 Nantes cedex 3 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
Abstract : OBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.
Document type :
Journal articles
Complete list of metadata
https://www.hal.inserm.fr/inserm-00719034
Contributor : Isabelle Baró Connect in order to contact the contributor
Submitted on : Wednesday, July 18, 2012 - 6:03:17 PM
Last modification on : Friday, December 3, 2021 - 12:12:51 PM
Long-term archiving on: : Friday, December 16, 2016 - 1:22:49 AM
Contributor : Isabelle Baró Connect in order to contact the contributor
Submitted on : Wednesday, July 18, 2012 - 6:03:17 PM
Last modification on : Friday, December 3, 2021 - 12:12:51 PM
Long-term archiving on: : Friday, December 16, 2016 - 1:22:49 AM
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Identifiers
- HAL Id : inserm-00719034, version 1
- DOI : 10.1016/j.jacc.2012.02.052
- PUBMED : 22766342
Collections
INSERM | UNIV-NANTES | UPMC | CNRS | LMJL | FMPL | THORAX-UMR | SORBONNE-UNIVERSITE | SU-TI
Citation
Gabriel Laurent, Samuel Saal, Mohamed Yassine Amarouch, Delphine Béziau, Roos Marsman, et al.. Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy.: MEPPC: a new SCN5A-related cardiac channelopathy. Journal of the American College of Cardiology, Elsevier, 2012, 60 (2), pp.144-56. ⟨10.1016/j.jacc.2012.02.052⟩. ⟨inserm-00719034⟩
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