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Employing tissue samples and cell lines derived from patients and animal models, omics approaches have revealed the myriad alterations in gene and microRNA expression, alternative splicing, 3\u2032 polyadenylation, CpG methylation, and proteins levels, among others, that contribute to this complex multisystem disease. In addition, omics characterization of drug candidate treatment experiments provides crucial insight into the degree of therapeutic rescue and off-target effects that can be achieved. Finally, several innovative technologies such as single-cell sequencing and artificial intelligence will have a significant impact on future DM1 research.<\/jats:p>","DOI":"10.3390\/ijms23031441","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T22:00:56Z","timestamp":1643320856000},"page":"1441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Deciphering the Complex Molecular Pathogenesis of Myotonic Dystrophy Type 1 through Omics Studies"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0098-5201","authenticated-orcid":false,"given":"Jorge","family":"Espinosa-Espinosa","sequence":"first","affiliation":[{"name":"University Research Institute for Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia, 46100 Valencia, Spain"},{"name":"Translational Genomics Group, Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchel","family":"Gonz\u00e1lez-Barriga","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Inserm, Institut de Myologie, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-2635","authenticated-orcid":false,"given":"Arturo","family":"L\u00f3pez-Castel","sequence":"additional","affiliation":[{"name":"University Research Institute for Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia, 46100 Valencia, Spain"},{"name":"Translational Genomics Group, Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-047X","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Artero","sequence":"additional","affiliation":[{"name":"University Research Institute for Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia, 46100 Valencia, Spain"},{"name":"Translational Genomics Group, Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000369343","article-title":"Prevalence of muscular dystrophies: A systematic literature review","volume":"43","author":"Theadom","year":"2014","journal-title":"Neuroepidemiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1045","DOI":"10.1212\/WNL.0000000000011425","article-title":"Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program","volume":"96","author":"Johnson","year":"2021","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s11910-005-0024-1","article-title":"Genetics and molecular pathogenesis of the myotonic dystrophies","volume":"5","author":"Day","year":"2005","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/ajmg.a.32987","article-title":"Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene","volume":"149A","author":"Musova","year":"2009","journal-title":"Am. J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1126\/science.1088679","article-title":"RNA leaching of transcription factors disrupts transcription in myotonic dystrophy","volume":"303","author":"Ebralidze","year":"2004","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1096\/fj.09-151159","article-title":"Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells","volume":"24","author":"Huichalaf","year":"2010","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nsmb.2067","article-title":"Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy","volume":"18","author":"Rau","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Mart\u00ednez, A., Soblechero-Mart\u00edn, P., de-la-Puente-Ovejero, L., Nogales-Gadea, G., and Arechavala-Gomeza, V. (2020). An Overview of Alternative Splicing Defects Implicated in Myotonic Dystrophy Type I. Genes, 11.","DOI":"10.3390\/genes11091109"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.molcel.2014.08.027","article-title":"Loss of MBNL Leads to Disruption of Developmentally Regulated Alternative Polyadenylation in RNA-Mediated Disease","volume":"56","author":"Batra","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20333","DOI":"10.1073\/pnas.0809045105","article-title":"A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart","volume":"105","author":"Kalsotra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1212\/CPJ.0000000000000531","article-title":"Consensus-based care recommendations for adults with myotonic dystrophy type 1","volume":"8","author":"Ashizawa","year":"2018","journal-title":"Neurol. Clin. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.drudis.2021.03.024","article-title":"Myotonic dystrophy type 1 drug development: A pipeline toward the market","volume":"26","author":"Artero","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/hmg\/11.7.805","article-title":"Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells","volume":"11","author":"Fardaei","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33779","DOI":"10.1074\/jbc.M110.124255","article-title":"RNA-binding protein Muscleblind-like 3 (MBNL3) disrupts myocyte enhancer factor 2 (Mef2) {beta}-exon splicing","volume":"285","author":"Lee","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1093\/nar\/gku767","article-title":"MBNL proteins and their target RNAs, interaction and splicing regulation","volume":"42","author":"Konieczny","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30999","DOI":"10.1038\/srep30999","article-title":"Muscleblind-like 3 deficit results in a spectrum of age-associated pathologies observed in myotonic dystrophy","volume":"6","author":"Choi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/wrna.107","article-title":"The importance of CELF control: Molecular and biological roles of the CUG-BP, Elav-like family of RNA-binding proteins: Importance of CELF control","volume":"3","author":"Dasgupta","year":"2012","journal-title":"WIREs RNA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nasiri-Aghdam, M., Garcia-Gardu\u00f1o, T.C., and Jave-Su\u00e1rez, L.F. (2021). CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein\/Noncoding RNA Regulatory Axis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011056"},{"key":"ref_19","unstructured":"Maloy, S., and Hughes, K. (2013). Alternative Splicing. Brenner\u2019s Encyclopedia of Genetics, Academic Press. [2nd ed.]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.14348\/molcells.2016.0035","article-title":"Alternative Polyadenylation of mRNAs: 3\u2032-Untranslated Region Matters in Gene Expression","volume":"39","author":"Yeh","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1101\/gad.17268411","article-title":"Ending the message: Poly(A) signals then and now","volume":"25","author":"Proudfoot","year":"2011","journal-title":"Genes Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.289.5485.1769","article-title":"Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat","volume":"289","author":"Mankodi","year":"2000","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gomes-Pereira, M., Foiry, L., Nicole, A., Huguet, A., Junien, C., Munnich, A., and Gourdon, G. (2007). CTG Trinucleotide Repeat \u201cBig Jumps\u201d: Large Expansions, Small Mice. PLoS Genet., 3.","DOI":"10.1371\/journal.pgen.0030052"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huguet, A., Medja, F., Nicole, A., Vignaud, A., Guiraud-Dogan, C., Ferry, A., Decostre, V., Hogrel, J.-Y., Metzger, F., and Hoeflich, A. (2012). Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1000 CTG Repeats from the Human DM1 Locus. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1003043"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1093\/brain\/aws367","article-title":"Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour","volume":"136","author":"Sicot","year":"2013","journal-title":"Brain"},{"key":"ref_27","first-page":"487","article-title":"Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds","volume":"10","author":"Arandel","year":"2017","journal-title":"Dis. Model Mech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: Ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"630","DOI":"10.2174\/1570159X16666180926123722","article-title":"Omics-based Biomarkers for the Early Alzheimer Disease Diagnosis and Reliable Therapeutic Targets Development","volume":"17","author":"Baquero","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"433","DOI":"10.14348\/molcells.2021.0042","article-title":"Integrative Multi-Omics Approaches in Cancer Research: From Biological Networks to Clinical Subtypes","volume":"44","author":"Heo","year":"2021","journal-title":"Mol. Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3389\/fnins.2020.577755","article-title":"From Multi-Omics Approaches to Precision Medicine in Amyotrophic Lateral Sclerosis","volume":"14","author":"Morello","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41588-021-00800-7","article-title":"Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics","volume":"53","author":"Bonder","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-genom-082908-145957","article-title":"Applications of New Sequencing Technologies for Transcriptome Analysis","volume":"10","author":"Morozova","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/chromsci\/bmw167","article-title":"Proteomics: Technologies and Their Applications","volume":"55","author":"Aslam","year":"2017","journal-title":"J. Chromatogr. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1126\/science.1088583","article-title":"A muscleblind knockout model for myotonic dystrophy","volume":"302","author":"Kanadia","year":"2003","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nsmb.1720","article-title":"Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy","volume":"17","author":"Du","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.gde.2011.03.006","article-title":"Decoding muscle alternative splicing","volume":"21","author":"Llorian","year":"2011","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.cell.2012.06.041","article-title":"Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins","volume":"150","author":"Wang","year":"2012","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18551","DOI":"10.1073\/pnas.0903234106","article-title":"Pentamidine reverses the splicing defects associated with myotonic dystrophy","volume":"106","author":"Warf","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1093\/nar\/gkab022","article-title":"Targeted splice sequencing reveals RNA toxicity and therapeutic response in myotonic dystrophy","volume":"49","author":"Tanner","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"bio058978","DOI":"10.1242\/bio.058978","article-title":"Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing","volume":"11","author":"Franck","year":"2022","journal-title":"Biol. Open"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/hmg\/ddy432","article-title":"Transcriptome alterations in myotonic dystrophy skeletal muscle and heart","volume":"28","author":"Wang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wagner, S.D., Struck, A.J., Gupta, R., Farnsworth, D.R., Mahady, A.E., Eichinger, K., Thornton, C.A., Wang, E.T., and Berglund, J.A. (2016). Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006316"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ana.23992","article-title":"Splicing biomarkers of disease severity in myotonic dystrophy","volume":"74","author":"Nakamori","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/cphy.c170002","article-title":"Myotonic Dystrophy and Developmental Regulation of RNA Processing","volume":"8","author":"Thomas","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/dvdy.24240","article-title":"Developmental insights into the pathology of and therapeutic strategies for DM1: Back to the basics: DM1 disease mechanisms and therapeutics","volume":"244","author":"Chau","year":"2015","journal-title":"Dev. Dyn."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.nmd.2013.11.001","article-title":"Most expression and splicing changes in myotonic dystrophy type 1 and type 2 skeletal muscle are shared with other muscular dystrophies","volume":"24","author":"Bachinski","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1002\/emmm.201303275","article-title":"Compound loss of muscleblind-like function in myotonic dystrophy","volume":"5","author":"Lee","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Andr\u00e9, L.M., van Cruchten, R.T.P., Willemse, M., Bezstarosti, K., Demmers, J.A.A., van Agtmaal, E.L., Wansink, D.G., and Wieringa, B. (2019). Recovery in the Myogenic Program of Congenital Myotonic Dystrophy Myoblasts after Excision of the Expanded (CTG)n Repeat. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225685"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/mus.20800","article-title":"Cerebral involvement in myotonic dystrophies","volume":"36","author":"Meola","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1016\/j.celrep.2017.06.006","article-title":"Downregulation of the Glial GLT1 Glutamate Transporter and Purkinje Cell Dysfunction in a Mouse Model of Myotonic Dystrophy","volume":"19","author":"Sicot","year":"2017","journal-title":"Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1093\/hmg\/ddh327","article-title":"Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons","volume":"13","author":"Jiang","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fncel.2017.00101","article-title":"Myotonic Dystrophies: State of the Art of New Therapeutic Developments for the CNS","volume":"11","author":"Gourdon","year":"2017","journal-title":"Front Cell Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.celrep.2015.07.029","article-title":"MBNL Sequestration by Toxic RNAs and RNA Mis-Processing in the Myotonic Dystrophy Brain","volume":"12","author":"Goodwin","year":"2015","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Azotla-Vilchis, C.N., Sanchez-Celis, D., Agonizantes-Ju\u00e1rez, L.E., Su\u00e1rez-S\u00e1nchez, R., Hern\u00e1ndez-Hern\u00e1ndez, J.M., Pe\u00f1a, J., V\u00e1zquez-Santill\u00e1n, K., Leyva-Garc\u00eda, N., Ortega, A., and Maldonado, V. (2021). Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1. Biomolecules, 11.","DOI":"10.3390\/biom11020159"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"662035","DOI":"10.3389\/fncel.2021.662035","article-title":"Integrative Cell Type-Specific Multi-Omics Approaches Reveal Impaired Programs of Glial Cell Differentiation in Mouse Culture Models of DM1","volume":"15","author":"Lallemant","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108634","DOI":"10.1016\/j.celrep.2020.108634","article-title":"Transcriptome alterations in myotonic dystrophy frontal cortex","volume":"34","author":"Otero","year":"2021","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Blech-Hermoni, Y., Dasgupta, T., Coram, R.J., and Ladd, A.N. (2016). Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149061"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1101\/gr.184390.114","article-title":"Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins","volume":"25","author":"Wang","year":"2015","journal-title":"Genome Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.celrep.2013.12.025","article-title":"The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue dramatically altering miRNA and mRNA expression","volume":"6","author":"Kalsotra","year":"2014","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.devcel.2020.01.037","article-title":"Aberrant Expression of a Non-muscle RBFOX2 Isoform Triggers Cardiac Conduction Defects in Myotonic Dystrophy","volume":"52","author":"Misra","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e143465","DOI":"10.1172\/jci.insight.143465","article-title":"Reversible cardiac disease features in an inducible CUG repeat RNA\u2013expressing mouse model of myotonic dystrophy","volume":"6","author":"Rao","year":"2021","journal-title":"JCI Insight"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/75490","article-title":"Mice deficient in Six5 develop cataracts: Implications for myotonic dystrophy","volume":"25","author":"Klesert","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/hmg\/ddr515","article-title":"Activation of the innate immune response and interferon signalling in myotonic dystrophy type 1 and type 2 cataracts","volume":"21","author":"Rhodes","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1567-133X(03)00064-4","article-title":"Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3","volume":"3","author":"Kanadia","year":"2003","journal-title":"Gene Expr. Patterns"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1038\/s41467-020-15962-x","article-title":"Loss of MBNL1 induces RNA misprocessing in the thymus and peripheral blood","volume":"11","author":"Sznajder","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.immuni.2018.04.015","article-title":"A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation","volume":"48","author":"Kernfeld","year":"2018","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nature10279","article-title":"A critical role for TCF-1 in T-lineage specification and differentiation","volume":"476","author":"Weber","year":"2011","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Visconti, V.V., Centofanti, F., Fittipaldi, S., Macr\u00ec, E., Novelli, G., and Botta, A. (2021). Epigenetics of Myotonic Dystrophies: A Minireview. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212594"},{"key":"ref_70","first-page":"38","article-title":"Elevated Global DNA Methylation Is Not Exclusive to Amyotrophic Lateral Sclerosis and Is Also Observed in Spinocerebellar Ataxia Types 1 and 2","volume":"18","author":"Hamzeiy","year":"2018","journal-title":"NDD"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"L\u00f3pez Castel, A., Overby, S.J., and Artero, R. (2019). MicroRNA-Based Therapeutic Perspectives in Myotonic Dystrophy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225600"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/s41419-018-0769-5","article-title":"High-throughput analysis of the RNA-induced silencing complex in myotonic dystrophy type 1 patients identifies the dysregulation of miR-29c and its target ASB2","volume":"9","author":"Cappella","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.omtm.2021.09.007","article-title":"miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1","volume":"23","author":"Koutalianos","year":"2021","journal-title":"Mol. Ther. -Methods Clin. Dev."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mateus, T., Martins, F., Nunes, A., Herdeiro, M.T., and Rebelo, S. (2021). Metabolic Alterations in Myotonic Dystrophy Type 1 and Their Correlation with Lipin. Int. J. Env. Res. Public Health, 18.","DOI":"10.3390\/ijerph18041794"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.lfs.2016.01.032","article-title":"Metabolic status of patients with muscular dystrophy in early phase of the disease: In vitro, high resolution NMR spectroscopy based metabolomics analysis of serum","volume":"151","author":"Srivastava","year":"2016","journal-title":"Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/jcmm.13543","article-title":"Cross-sectional serum metabolomic study of multiple forms of muscular dystrophy","volume":"22","author":"Spitali","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.drudis.2018.08.004","article-title":"RNA-mediated therapies in myotonic dystrophy","volume":"23","author":"Overby","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1242\/dmm.018127","article-title":"Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model","volume":"8","author":"Bargiela","year":"2015","journal-title":"Dis. Model Mech."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.omtn.2019.11.012","article-title":"miR-7 Restores Phenotypes in Myotonic Dystrophy Muscle Cells by Repressing Hyperactivated Autophagy","volume":"19","author":"Bargiela","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"25203","DOI":"10.1073\/pnas.1820297116","article-title":"Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models","volume":"116","author":"Bargiela","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/acn3.271","article-title":"Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy","volume":"3","author":"Nakamori","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1021\/acsptsci.9b00020","article-title":"Combination Treatment of Erythromycin and Furamidine Provides Additive and Synergistic Rescue of Mis-splicing in Myotonic Dystrophy Type 1 Models","volume":"2","author":"Jenquin","year":"2019","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1038\/mtna.2015.35","article-title":"In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin","volume":"4","author":"Laustriat","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.omtn.2017.05.007","article-title":"Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice","volume":"7","author":"Jauvin","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41467-018-04892-4","article-title":"miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models","volume":"9","author":"Moreno","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.omtn.2021.07.017","article-title":"Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy","volume":"26","author":"Moreno","year":"2021","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1096\/fj.201700700R","article-title":"Correction of GSK3\u03b2 at young age prevents muscle pathology in mice with myotonic dystrophy type 1","volume":"32","author":"Wei","year":"2018","journal-title":"FASEB J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1093\/nar\/gky548","article-title":"Efficient CRISPR\/Cas9-mediated editing of trinucleotide repeat expansion in myotonic dystrophy patient-derived iPS and myogenic cells","volume":"46","author":"Dastidar","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ymthe.2021.08.004","article-title":"Comprehensive transcriptome-wide analysis of spliceopathy correction of myotonic dystrophy using CRISPR-Cas9 in iPSCs-derived cardiomyocytes","volume":"30","author":"Dastidar","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1093\/hmg\/dds185","article-title":"Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity","volume":"21","author":"Morales","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/gim.2017.86","article-title":"Long-read genome sequencing identifies causal structural variation in a Mendelian disease","volume":"20","author":"Merker","year":"2018","journal-title":"Genet. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1093\/brain\/awz115","article-title":"MSH3 modifies somatic instability and disease severity in Huntington\u2019s and myotonic dystrophy type 1","volume":"142","author":"Flower","year":"2019","journal-title":"Brain"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s10038-019-0671-8","article-title":"Long-read sequencing for rare human genetic diseases","volume":"65","author":"Mitsuhashi","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s40478-021-01201-x","article-title":"An update on the neurological short tandem repeat expansion disorders and the emergence of long-read sequencing diagnostics","volume":"9","author":"Chintalaphani","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.cell.2015.02.014","article-title":"The RNA Binding Protein Quaking Regulates Formation of circRNAs","volume":"160","author":"Conn","year":"2015","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3389\/fgene.2019.00649","article-title":"Global Increase in Circular RNA Levels in Myotonic Dystrophy","volume":"10","author":"Czubak","year":"2019","journal-title":"Front. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1441\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:08:48Z","timestamp":1760134128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":99,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031441"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031441","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,27]]}}}