{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:17:01Z","timestamp":1771489021816,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AP-HM"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Exon skipping is a promising therapeutic approach. One important condition for this approach is that the exon-skipped form of the gene can at least partially perform the required function and lead to improvement of the phenotype. It is therefore critical to identify the exons that can be skipped without a significant deleterious effect on the protein function. Pathogenic variants in the DMD gene are responsible for Duchenne muscular dystrophy (DMD). We report for the first time a deletion of the in-frame exon 49 associated with a strikingly normal muscular phenotype. Based on this observation, and on previously known therapeutic approaches using exon skipping in DMD for other single exons, we aimed to extend the clinical use of exon skipping for patients carrying truncating mutations in exon 49. We first determined the precise genomic position of the exon 49 deletion in our patients. We then demonstrated the feasibility of skipping exon 49 using an in vitro AON (antisense oligonucleotide) approach in human myotubes carrying a truncating pathogenic variant as well as in healthy ones. This work is a proof of concept aiming to expand exon-skipping approaches for DMD exon 49.<\/jats:p>","DOI":"10.3390\/genes13071277","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T23:10:22Z","timestamp":1658272222000},"page":"1277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel Exon-Skipping Therapeutic Approach for the DMD Gene Based on Asymptomatic Deletions of Exon 49"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1562-2024","authenticated-orcid":false,"given":"Mario","family":"Abaji","sequence":"first","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Gorokhova","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Da Silva","sequence":"additional","affiliation":[{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Busa","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-9147","authenticated-orcid":false,"given":"Maude","family":"Grelet","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Inter-Communal Toulon-La Seyne, Medical Genetics Unit, Sainte Musse Hospital, 83100 Toulon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Missirian","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Sigaudy","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Philip","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"France","family":"Leturcq","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, APHP Centre Universit\u00e9 Paris Cit\u00e9 Cochin Hospital, 75014 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"L\u00e9vy","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Krahn","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"},{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-9858","authenticated-orcid":false,"given":"Marc","family":"Bartoli","sequence":"additional","affiliation":[{"name":"MMG, INSERM, Aix Marseille University, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ana.23528","article-title":"Evidence-Based Path to Newborn Screening for Duchenne Muscular Dystrophy","volume":"71","author":"Mendell","year":"2012","journal-title":"Ann. 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