, Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3??? end of a transcript encoding a protein kinase family member, Cell, vol.68, issue.4, pp.799-808, 1992.
DOI : 10.1016/0092-8674(92)90154-5
, An unstable triplet repeat in a gene related to myotonic muscular dystrophy, Science, vol.255, issue.5049, pp.1256-1258, 1992.
DOI : 10.1126/science.1546326
, Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene, Science, vol.255, issue.5049, pp.1253-1255, 1992.
DOI : 10.1126/science.1546325
, Myotonic Dystrophy Type 2 Caused by a CCTG Expansion in Intron 1 of ZNF9, Science, vol.293, issue.5531, pp.864-867, 2001.
DOI : 10.1126/science.1062125
, Recruitment of human muscleblind proteins to (CUG)n expansions associated with myotonic dystrophy, The EMBO Journal, vol.19, issue.17, pp.4439-4448, 2000.
DOI : 10.1093/emboj/19.17.4439
, A Muscleblind Knockout Model for Myotonic Dystrophy, Science, vol.302, issue.5652, pp.1978-1980, 2003.
DOI : 10.1126/science.1088583
, Increased Steady-State Levels of CUGBP1 in Myotonic Dystrophy 1 Are Due to PKC-Mediated Hyperphosphorylation, Molecular Cell, vol.28, issue.1, pp.68-78, 2007.
DOI : 10.1016/j.molcel.2007.07.027
, Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy, Nature Genetics, vol.29, issue.1, pp.40-47, 2001.
DOI : 10.1038/ng704
, Expanded CUG Repeats Trigger Aberrant Splicing of ClC-1 Chloride Channel Pre-mRNA and Hyperexcitability of Skeletal Muscle in Myotonic Dystrophy, Molecular Cell, vol.10, issue.1, pp.35-44, 2002.
DOI : 10.1016/S1097-2765(02)00563-4
, Loss of the Muscle-Specific Chloride Channel in Type 1 Myotonic Dystrophy Due to Misregulated Alternative Splicing, Molecular Cell, vol.10, issue.1, pp.45-53, 2002.
DOI : 10.1016/S1097-2765(02)00572-5
, Altered mRNA splicing of dystrophin in type 1 myotonic dystrophy, Muscle & Nerve, vol.12, issue.2, pp.251-257, 2007.
DOI : 10.1002/mus.20809
, Abnormal splicing switch of DMD???s penultimate exon compromises muscle fibre maintenance in myotonic dystrophy, Nature Communications, vol.10, p.7205, 2015.
DOI : 10.1038/ncomms8205
, Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy, Nature Medicine, vol.279, issue.6, pp.720-725, 2011.
DOI : 10.1016/j.neures.2006.05.002
URL : https://hal.archives-ouvertes.fr/hal-00811986
, Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1, Human Molecular Genetics, vol.14, issue.15, pp.2189-2200, 2005.
DOI : 10.1093/hmg/ddi223
, Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of CaV1.1 calcium channel, Human Molecular Genetics, vol.21, issue.6, pp.1312-1324, 2012.
DOI : 10.1093/hmg/ddr568
, Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy, Journal of Clinical Investigation, vol.117, pp.3952-3957, 2007.
DOI : 10.1172/JCI33355
, Electrocardiographic Abnormalities and Sudden Death in Myotonic Dystrophy Type 1, New England Journal of Medicine, vol.358, issue.25, pp.2688-2697, 2008.
DOI : 10.1056/NEJMoa062800
, Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing, Journal of the American College of Cardiology, vol.40, issue.9, pp.1645-1652, 2002.
DOI : 10.1016/S0735-1097(02)02339-2
, Genetic basis and molecular mechanism for idiopathic ventricular fibrillation, Nature, vol.392, pp.293-296, 1998.
, A sodium-channel mutation causes isolated cardiac conduction disease, Nature, vol.409, issue.6823, pp.1043-1047, 2001.
DOI : 10.1038/35059090
, Cardiac conduction defects associate with mutations in SCN5A, Nature Genetics, vol.23, issue.1, pp.20-21, 1999.
DOI : 10.1038/12618
, Detecting differential usage of exons from RNA-seq data, Genome Res, vol.22, 2008.
, Analysis and design of RNA sequencing experiments for identifying isoform regulation, Nature Methods, vol.90, issue.12, pp.1009-1015, 2010.
DOI : 10.1038/nmeth.1528
, Disruption of Splicing Regulated by a CUG-Binding Protein in Myotonic Dystrophy, Science, vol.280, issue.5364, pp.737-741, 1998.
DOI : 10.1126/science.280.5364.737
, Splicing biomarkers of disease severity in myotonic dystrophy, Annals of Neurology, vol.46, issue.6, pp.862-872, 2013.
DOI : 10.1002/ana.23992
, A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart, Proc. Natl Acad. Sci. USA 105, pp.20333-20338, 2008.
DOI : 10.1073/pnas.0809045105
, Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans, Journal of Clinical Investigation, vol.115, issue.9, pp.2462-2471, 2005.
DOI : 10.1172/JCI23853
, Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene, Proc. Natl Acad. Sci. USA 103, pp.5084-5089, 2006.
DOI : 10.1073/pnas.0600548103
, Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs, Nucleic Acids Research, vol.35, issue.16, pp.5474-5486, 2007.
DOI : 10.1093/nar/gkm601
, Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats, Human Molecular Genetics, vol.13, issue.5, pp.495-507, 2004.
DOI : 10.1093/hmg/ddh056
, MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing, Nucleic Acids Research, vol.38, issue.7, pp.2467-2484, 2010.
DOI : 10.1093/nar/gkp1209
, Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1, Nature Structural & Molecular Biology, vol.276, issue.12, pp.1343-1351, 2008.
DOI : 10.1016/0014-5793(72)80067-X
, CUG-BP1/CELF1 requires UGU-rich sequences for high-affinity binding, Biochemical Journal, vol.400, issue.2, pp.291-301, 2006.
DOI : 10.1042/BJ20060490
URL : https://hal.archives-ouvertes.fr/hal-00478569
, Structural Insights into RNA Recognition by the Alternate-Splicing Regulator CUG-Binding Protein 1, Structure, vol.18, issue.10, pp.1364-1377, 2010.
DOI : 10.1016/j.str.2010.06.018
, Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins, Cell, vol.150, issue.4, pp.710-724, 2012.
DOI : 10.1016/j.cell.2012.06.041
, MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain, Cell Reports, vol.12, issue.7, pp.1159-1168, 2015.
DOI : 10.1016/j.celrep.2015.07.029
, Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy, Human Molecular Genetics, vol.15, issue.13, pp.2087-2097, 2006.
DOI : 10.1093/hmg/ddl132
, Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy, Proceedings of the National Academy of Sciences, vol.103, issue.31
DOI : 10.1073/pnas.0604970103
, Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia. Heart Rhythm, pp.590-597, 2012.
, Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels, PLoS ONE, vol.216, issue.4, p.19188, 2011.
DOI : 10.1371/journal.pone.0019188.t003
, Alternative splicing of Nav1.5: An electrophysiological comparison of ???neonatal??? and ???adult??? isoforms and critical involvement of a lysine residue, Journal of Cellular Physiology, vol.279, issue.3, pp.716-726, 2008.
DOI : 10.1002/jcp.21451
, Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1, Archives of Cardiovascular Diseases, vol.106, issue.12, pp.635-643, 2013.
DOI : 10.1016/j.acvd.2013.08.003
, Compound loss of muscleblind-like function in myotonic dystrophy, EMBO Molecular Medicine, vol.41, issue.12, pp.1887-1900, 2013.
DOI : 10.1002/emmm.201303275
, Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms, Scientific Reports, vol.174, p.9042, 2015.
DOI : 10.1038/srep09042
, Variable Nav1.5 Protein Expression from the Wild-Type Allele Correlates with the Penetrance of Cardiac Conduction Disease in the Scn5a+/??? Mouse Model, PLoS ONE, vol.290, issue.2, p.9298, 2010.
DOI : 10.1371/journal.pone.0009298.t003
, Mouse Model of SCN5A-Linked Hereditary Lenegre's Disease: Age-Related Conduction Slowing and Myocardial Fibrosis, Circulation, vol.111, issue.14, pp.1738-1746, 2005.
DOI : 10.1161/01.CIR.0000160853.19867.61
, Impaired Impulse Propagation in Scn5a-Knockout Mice: Combined Contribution of Excitability, Connexin Expression, and Tissue Architecture in Relation to Aging, Circulation, vol.112, issue.13, pp.1927-1935, 2005.
DOI : 10.1161/CIRCULATIONAHA.105.539072
, Simulation of the Undiseased Human Cardiac Ventricular Action
Potential: Model Formulation and Experimental Validation, PLoS Computational Biology, vol.93, issue.Pt2, p.1002061, 2011.
DOI : 10.1371/journal.pcbi.1002061.s001
, Identification and functional characterization of KCNQ1 mutations around the exon 7???intron 7 junction affecting the splicing process, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol.1812, issue.11, pp.1452-1459, 2011.
DOI : 10.1016/j.bbadis.2011.07.011
, One-Dimensional Mathematical Model of the Atrioventricular Node Including Atrio-Nodal, Nodal, and Nodal-His Cells, Biophysical Journal, vol.97, issue.8, pp.2117-2127, 2009.
DOI : 10.1016/j.bpj.2009.06.056
, Progressive Cardiac Conduction Defect is the Prevailing Phenotype in Carriers of a Brugada Syndrome SCN5A Mutation, Journal of Cardiovascular Electrophysiology, vol.14, issue.3, pp.270-275, 2006.
DOI : 10.1161/01.CIR.0000160853.19867.61
URL : https://hal.archives-ouvertes.fr/hal-00750431
, Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease, AJP: Heart and Circulatory Physiology, vol.292, issue.1, pp.399-407, 2007.
DOI : 10.1152/ajpheart.01025.2005
, Clinical, Genetic, and Biophysical Characterization of SCN5A Mutations Associated With Atrioventricular Conduction Block, Circulation, vol.105, issue.3, pp.341-346, 2002.
DOI : 10.1161/hc0302.102592
, Brugada-like cardiac disease in myotonic dystrophy type 2: report of two unrelated patients, European Journal of Neurology, vol.21, issue.1, pp.191-194, 2011.
DOI : 10.1111/j.1468-1331.2010.03077.x
, Unmasked Brugada Pattern by Ajmaline Challenge in Patients with Myotonic Dystrophy Type 1, Annals of Noninvasive Electrocardiology, vol.82, issue.1, pp.28-36, 2015.
DOI : 10.1111/anec.12168
, Prevalence of type 1 Brugada ECG pattern after administration of Class 1C drugs in patients with type 1 myotonic dystrophy: Myotonic dystrophy as a part of the Brugada syndrome, Heart Rhythm, vol.11, issue.10, pp.1721-1727, 2014.
DOI : 10.1016/j.hrthm.2014.07.011
, Abnormal sodium current properties contribute to cardiac electrical and contractile dysfunction in a mouse model of myotonic dystrophy type 1, Neuromuscular Disorders, vol.25, issue.4, pp.308-320, 2014.
DOI : 10.1016/j.nmd.2014.11.018
, RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression, Nature Genetics, vol.25, issue.1, pp.61-68, 2008.
DOI : 10.1038/ng.2007.28
, Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1, Human Molecular Genetics, vol.19, issue.6, pp.1066-1075, 2010.
DOI : 10.1093/hmg/ddp570
, The Mef2 Transcription Network Is Disrupted in Myotonic Dystrophy Heart Tissue, Dramatically Altering miRNA and mRNA Expression, Cell Reports, vol.6, issue.2, pp.336-345, 2014.
DOI : 10.1016/j.celrep.2013.12.025
, Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy, Nature Structural & Molecular Biology, vol.63, issue.7, pp.840-845, 2011.
DOI : 10.1212/01.wnl.0000302174.08951.cf
, A Cautionary Tale, Journal of Clinical Neuromuscular Disease, vol.7, issue.1, pp.25-28, 2005.
DOI : 10.1097/01.cnd.0000174372.19888.41
, Arrhythmia exacerbation after sodium channel blockade in myotonic dystrophy type 1, Muscle & Nerve, vol.1, issue.5, pp.901-902, 2009.
DOI : 10.1002/mus.21345
, Familial clustering of muscular and cardiac involvement in myotonic dystrophy type 1, Muscle & Nerve, vol.1, issue.6, pp.719-724, 2005.
DOI : 10.1002/mus.20310
, Myotonic dystrophy type 1 mimics and exacerbates Brugada phenotype induced by Nav1.5 sodium channel loss-of-function mutation, Heart Rhythm, vol.11, issue.8, pp.1393-1400, 2014.
DOI : 10.1016/j.hrthm.2014.04.026
URL : https://hal.archives-ouvertes.fr/hal-00992887
, Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules, Nature Communications, vol.53, p.2044, 2013.
DOI : 10.1038/ncomms3044
, Targeting nuclear RNA for in vivo correction of myotonic dystrophy, Nature, vol.274, issue.7409, pp.111-115, 2012.
DOI : 10.1038/nature11362
, Aberrantly spliced ??-dystrobrevin alters ??-syntrophin binding in myotonic dystrophy type 1, Neurology, vol.70, issue.9, pp.677-685, 2008.
DOI : 10.1212/01.wnl.0000302174.08951.cf
, Sudden cardiac death in myotonic dystrophy type 2, Neurology, vol.63, issue.12, pp.2402-2404, 2004.
DOI : 10.1212/01.WNL.0000147335.10783.E4
, Proximal myotonic dystrophy???a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes?, Neuromuscular Disorders, vol.7, issue.4, pp.217-228, 1997.
DOI : 10.1016/S0960-8966(97)00041-2
, TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions, Genome Biology, vol.14, issue.4, p.36, 2013.
DOI : 10.1186/gb-2009-10-3-r25
, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nature Biotechnology, vol.25, issue.5, pp.511-515, 2010.
DOI : 10.1038/nbt.1621
, Rescue of Dystrophic Muscle Through U7 snRNA-Mediated Exon Skipping, Science, vol.306, issue.5702, pp.1796-1799, 2004.
DOI : 10.1126/science.1104297
, ) for the gift of the pGEX-MBNL1D 101 vector, the Research Resource Network Japan and the Myobank of the Institute of Myology for providing human heart tissue samples, Feriel Azibani (UMRS974, Paris, France) and all members of the French DM Network for fruitful discussion. We also deeply thank the IGBMC Microarray and Sequencing platform, the informatics resources of the PRABI, Nathalie Mougenot from the UPMC PECMV-CEF facility, the Fédération de Recherche en Imagerie Multimodalité (www.bichat.inserm.fr), the AAV platform of the Centre de Recherche en Myologie, the Penn Vector Core, Gene Therapy Program, University of Pennsylvania (Philadelphia) for providing the pAAV2/9 plasmid (p5E18-VD29), members of the France Genomique program for RNA sequencing and all IGBMC common facilities for assistance, ) for the gift of the DT960 and tgCUGBP1 plasmids This work was supported by UPMC/INSERM/CNRS/AIM (D.F.)
, 2012-StG #310659 'RNA DISEASES' and ANR-10-LABX-0030-INRT and ANR-10-IDEX-0002-02