ArticleNature communications2016
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
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Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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126citing papers in PubMed, 1 pooled it
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Clinical Care Recommendations for Cardiologists Treating Adults With Myotonic Dystrophy.Journal of the American Heart Association · 2020Guideline
- Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood.BMC medicine · 2022Trial
- DMPK 3' untranslated repeat expansions in unexplained sudden cardiac death in the young.European heart journal · 2026Article
- RNA splicing and cardiovascular disease: a guide for cardiologists.European heart journal · 2026Review
- The dark genome in cardiovascular medicine.European heart journal · 2026Review
- CRISPR/dCas9-mediated tuning of DMPK transcription reveals a quantitative relationship between toxic repeat RNA expression and MBNL1 activity in myotonic dystrophy.Human molecular genetics · 2026Article
- MBNL depletion drives stem cell fusion and immature myonuclear states in myotonic dystrophy type 1.Nature communications · 2026Article
- Mapping of CELF1-RNA interactions reveals post-transcriptional control of lens development.NAR molecular medicine · 2026Article
- Current biomarker development in myotonic dystrophies.Journal of neurology · 2026Review
- Current Topics of Progressive Cardiac Conduction Disease.Journal of arrhythmia · 2026Review
- Sex Differences in Cardiac Involvement in Adults With Myotonic Dystrophy Type 1: A Multicenter Study.JACC. Advances · 2026Article
- Changes in RNA splicing as a surrogate endpoint for myotonic dystrophy Type 1 (DM1) clinical trials.Journal of neuromuscular diseases · 2026Review
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- Disruptions of cell signaling pathways in myotonic dystrophy type 1 skeletal muscle, their pathogenic impact, and potential for combinatorial therapeutics.The Journal of biological chemistry · 2026Review
- Aberrant Splicing ofCirculation. Genomic and precision medicine · 2026Article
- Mapping of CELF1-RNA interactions reveals post-transcriptional control of lens development.bioRxiv : the preprint server for biology · 2026Article
- Ancestral intronic splicing regulatory elements in the SCNbioRxiv : the preprint server for biology · 2026Article
- Quantitative susceptibility mapping in myotonic dystrophy: clinical relevance of subcortical iron accumulation.Brain communications · 2026Article
- A novel discovery of elevated risk of neuroendocrine tumors in patients with myotonic dystrophy.Journal of the neurological sciences · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 20 institutions in 8 countries.
Fernande FreyermuthDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Frédérique RauSorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie UMRS974/FRE3617, Institut de Myologie, GH Pitié-Salpêtrière, Paris 75013, France.
Yosuke KokunaiDepartment of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Thomas LinkeDepartment of Physiology, Friedrich Schiller University Hospital, Jena 07743, Germany.
Chantal SellierDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Masayuki NakamoriDepartment of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Yoshihiro KinoDepartment of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose 205-8588, Japan.
Ludovic ArandelSorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie UMRS974/FRE3617, Institut de Myologie, GH Pitié-Salpêtrière, Paris 75013, France.
Arnaud JolletSorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie UMRS974/FRE3617, Institut de Myologie, GH Pitié-Salpêtrière, Paris 75013, France.
Christelle ThibaultDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Muriel PhilippsDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Serge VicaireDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Bernard JostDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Bjarne UddNeuromuscular Research Center, Tampere University and University Hospital, Tampere 33520, Finland.
John W DayDepartment of Neurology, Stanford University, Stanford, California 94304, USA.
Denis DubocService de Cardiologie, Université Paris-Descartes, Hôpital Cochin, AP-HP, Paris 75014, France.
Karim WahbiService de Cardiologie, Université Paris-Descartes, Hôpital Cochin, AP-HP, Paris 75014, France.
Tsuyoshi MatsumuraDepartment of Neurology, Toneyama National Hospital, Toyonaka 560-8552, Japan.
Harutoshi FujimuraDepartment of Neurology, Toneyama National Hospital, Toyonaka 560-8552, Japan.
Hideki MochizukiDepartment of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.ORCID http://orcid.org/0000-0002-0874-7542
François DeryckereCNRS UMR7175, Ecole Supérieure de Biotechnologies de Strasbourg, Illkirch 67400, France.
Takashi KimuraDivision of Neurology, Hyogo Medical College, Nishinomiya 663-8501, Japan.
Nobuyuki NukinaLaboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science, Kyoto 610-0394, Japan.
Shoichi IshiuraGraduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan.
Vincent LacroixUniversité Lyon 1, CNRS, UMR5558 LBBE, Villeurbanne 69622, France.
Amandine Campan-FournierHospices civils de Lyon, Laboratoire de cytogénétique constitutionelle, Bron 69500, France.
Vincent NavratilPôle Rhône Alpes de Bioinformatique, Université Lyon 1, Bâtiment Gregor Mendel, Villeurbanne 69100, France.
Emilie ChautardCentre de Recherche en Cancérologie de Lyon, Lyon 69373, France.ORCID http://orcid.org/0000-0003-1456-5347
Didier AuboeufCentre de Recherche en Cancérologie de Lyon, Lyon 69373, France.
Minoru HorieDepartment of Cardiovascular and Respiratory Medicine, Shiga Medical University, Otsu 520-2192, Japan.
Keiji ImotoDepartment of Information Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
Kuang-Yung LeeDepartment of Neurology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan.
Maurice S SwansonDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610, USA.
Adolfo Lopez de MunainDepartment of Neurology, Hospital Universitario DONOSTIA, Neuroscience Area, Institute Biodonostia CIBERNED and University of Basque Country UPV-EHU, San Sebastián 20014, Spain.
Shin InadaLaboratory of Biomedical Sciences and Information Management, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan.
Hideki ItohDepartment of Cardiovascular and Respiratory Medicine, Shiga Medical University, Otsu 520-2192, Japan.
Kazuo NakazawaLaboratory of Biomedical Sciences and Information Management, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan.
Takashi AshiharaDepartment of Cardiovascular and Respiratory Medicine, Shiga Medical University, Otsu 520-2192, Japan.
Eric WangDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610, USA.
Thomas ZimmerDepartment of Physiology, Friedrich Schiller University Hospital, Jena 07743, Germany.
Denis FurlingSorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, Centre de Recherche en Myologie UMRS974/FRE3617, Institut de Myologie, GH Pitié-Salpêtrière, Paris 75013, France.
Masanori P TakahashiDepartment of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Nicolas Charlet-BerguerandDepartment of Translational medicine and neurogenetics, IGBMC, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67400, France.
Centre National de la Recherche Scientifique · FRThe University of Osaka · JPShiga University of Medical Science · JPCentre de Recherche en Cancérologie de Lyon · FRFriedrich Schiller University Jena · DENational Cerebral and Cardiovascular Center · JPToneyama National Hospital · JPUniversité Claude Bernard Lyon 1 · FRUniversité Paris Cité · FRUniversity of Florida · USBiogipuzkoa Health Research Institute · ESChang Gung Memorial Hospital · TWDoshisha University · JPHospices Civils de Lyon · FRHyogo Medical University · JPMeiji Pharmaceutical University · JPNational Institute for Physiological Sciences · JPStanford University · USTokyo University of the Arts · JPUniversity of Helsinki · FI
Funding
Temporal/spatial RNA Expression Effects in DM1 and DM2P01NS058901 · NINDS · UNIVERSITY OF MINNESOTA · PI RANUM, LAURA P.W · 2008 to 2017
$12.3MPpst-transcriptional regulation of gene expression in neuromuscular diseaseDP5OD017865 · OD · UNIVERSITY OF FLORIDA · PI WANG, ERIC T · 2013 to 2017
$2.0MEuropean Research Council 310659NIH HHS DP5 OD017865NINDS NIH HHS P01 NS058901
Abstract
Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a reduced excitability compared with the control adult isoform. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy.
Indexed as
AdultAgedAlternative SplicingAnimalsArrhythmias, CardiacBase SequenceBinding SitesComputer SimulationElectrophysiological PhenomenaExonsFemaleHeart Conduction SystemHEK293 CellsHumansMaleMiddle AgedNAV1.5 Voltage-Gated Sodium ChannelRNA-Binding ProteinsSCN5A protein, humanSodium Channels
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