{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:38:49Z","timestamp":1787315929641,"version":"build-2736575974"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"am","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>More than 50 repeat expansion disorders have been identified, with long-read sequencing marking a new milestone in the diagnosis of these disorders. Despite these major achievements, the comprehensive characterization of short tandem repeats in a pathological context remains challenging, primarily due to their inherent characteristics such as motif complexity, high GC content, and variable length. In this study, our aim was to thoroughly characterize repeat expansions in two neuromuscular diseases: myotonic dystrophy type 1 (DM1) and oculopharyngodistal myopathy (OPDM) using CRISPR\/Cas9-targeted long-read sequencing (Oxford Nanopore Technologies, ONT). We conducted precise analyses of the DM1 and OPDM loci, determining repeat size, repeat length distribution, expansion architecture, and DNA methylation, using three different basecalling strategies (MinKnow software, Dorado, and Bonito). We demonstrated the importance of the basecalling strategy in repeat expansion characterization. We proposed guidelines to perform CRISPR-Cas9 targeted long-read sequencing (no longer supported by ONT), from library preparation to bioinformatical analyses. Finally, we showed, for the first time, somatic mosaicism, hypermethylation of LRP12 locus in OPDM symptomatic patients and changes in the repeat tract structure of these patients. We propose a strategy based on CRISPR\/Cas9-enrichment long-read sequencing for repeat expansion diseases, which can be readily applicable not only in research but also in diagnostic settings.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzaf094","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:11:44Z","timestamp":1761282704000},"source":"Crossref","is-referenced-by-count":7,"title":["Comparative Analysis of CRISPR\/Cas9-targeted Nanopore Sequencing Approaches in Repeat Expansion Disorders"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-9170","authenticated-orcid":false,"given":"Louise","family":"Benarroch","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-8232","authenticated-orcid":false,"given":"Pierre-Yves","family":"Bo\u00eblle","sequence":"additional","affiliation":[{"name":"Universit\u00e9 (CINBIOS) Sorbonne Universit\u00e9, UMS Pass, Center for Informatics-Bioanalysis Sorbonne , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-4400","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Madry","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, UMS Pass, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re (P3S) , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-094X","authenticated-orcid":false,"given":"Badreddine","family":"Mohand Oumoussa","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, UMS Pass, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re (P3S) , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-3152","authenticated-orcid":false,"given":"Nobuyuki","family":"Eura","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Center of Neurology and Psychiatry (NCNP) , Tokyo 187-8502,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Center of Neurology and Psychiatry (NCNP) , Tokyo 187-8502,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6549-9933","authenticated-orcid":false,"given":"Karim","family":"Labr\u00e8che","sequence":"additional","affiliation":[{"name":"Universit\u00e9 (CINBIOS) Sorbonne Universit\u00e9, UMS Pass, Center for Informatics-Bioanalysis Sorbonne , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0811-478X","authenticated-orcid":false,"given":"Valeriia","family":"Gorbunova","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2044-1052","authenticated-orcid":false,"given":"Guillaume","family":"Bassez","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]},{"name":"Assistance Publique-H\u00f4pitaux de Paris Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires Nord-Est\/\u00cele-de-France, Institut de Myologie, GHU Piti\u00e9-Salp\u00eatri\u00e8re, , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-2838","authenticated-orcid":false,"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]},{"name":"Assistance Publique-H\u00f4pitaux de Paris Centre de R\u00e9f\u00e9rence des Maladies Neuromusculaires Nord-Est\/\u00cele-de-France, Institut de Myologie, GHU Piti\u00e9-Salp\u00eatri\u00e8re, , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3319-1347","authenticated-orcid":false,"given":"Genevi\u00e8ve","family":"Gourdon","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-3258","authenticated-orcid":false,"given":"Gis\u00e8le","family":"Bonne","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-9256","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Tom\u00e9","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Centre de Recherche en myologie , Paris 75013,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,22]]},"container-title":["Genomics, Proteomics &amp; 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