{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:06:50Z","timestamp":1775617610726,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Duchenne muscular dystrophy (DMD) is an incurable disease caused by out-of-frame DMD gene deletions while in frame deletions lead to the milder Becker muscular dystrophy (BMD). In the last decade several antisense oligonucleotides drugs have been developed to induce a partially functional internally deleted dystrophin, similar to that produced in BMD, and expected to ameliorate the disease course. The pattern of dystrophin expression and functionality in dystrophinopathy patients is variable due to multiple factors, such as molecular functionality of the dystrophin and its distribution. To benchmark the success of therapeutic intervention, a clear understanding of dystrophin expression patterns in dystrophinopathy patients is vital. Recently, several groups have used innovative techniques to quantify dystrophin in muscle biopsies of children but not in patients with milder BMD. This study reports on dystrophin expression using both Western blotting and an automated, high-throughput, image analysis platform in DMD, BMD, and intermediate DMD\/BMD skeletal muscle biopsies. Our results found a significant correlation between Western blot and immunofluorescent quantification indicating consistency between the different methodologies. However, we identified significant inter- and intradisease heterogeneity of patterns of dystrophin expression in patients irrespective of the amount detected on blot, due to variability in both fluorescence intensity and dystrophin sarcolemmal circumference coverage. Our data highlight the heterogeneity of the pattern of dystrophin expression in BMD, which will assist the assessment of dystrophin restoration therapies.<\/jats:p>","DOI":"10.1093\/jnen\/nlab088","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T07:57:56Z","timestamp":1631174276000},"page":"955-965","source":"Crossref","is-referenced-by-count":13,"title":["High-Throughput Digital Image Analysis Reveals Distinct Patterns of Dystrophin Expression in Dystrophinopathy Patients"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8840-6835","authenticated-orcid":false,"given":"Silvia","family":"Torelli","sequence":"first","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"},{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenic","family":"Scaglioni","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Sardone","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J","family":"Ellis","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Domingos","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Jones","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Feng","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Queen Square Institute of Neurology & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Chambers","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah M","family":"Eastwood","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Great Ormond Street Hospital , London, UK"},{"name":"The Royal National Orthopaedic Hospital, Stanmore and University College London , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"France","family":"Leturcq","sequence":"additional","affiliation":[{"name":"APHP, Laboratoire de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaire, HUPC H\u00f4pital Cochin , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabah Ben","family":"Yaou","sequence":"additional","affiliation":[{"name":"APHP, Laboratoire de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaire, HUPC H\u00f4pital Cochin , Paris, France"},{"name":"APHP-Sorbonne Universit\u00e9, Centre de R\u00e9f\u00e9rence Maladies Neuromusculaires Nord\/Est\/Ile de France, Institut de Myologie, GH Piti\u00e9-Salp\u00eatri\u00e8re , Paris, France"},{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Center de Recherche en Myologie , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andoni","family":"Urtizberea","sequence":"additional","affiliation":[{"name":"APHP-H\u00f4pital Marin de Hendaye , Hendaye, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Sabouraud","sequence":"additional","affiliation":[{"name":"CHU de Reims\u2014American Memorial Hospital , Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Barnerias","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Necker Enfants Maladies Hospital , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut de Myologie, Center de Recherche en Myologie , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enzo","family":"Ricci","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Catholic University , Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maud","family":"Beuvin","sequence":"additional","affiliation":[{"name":"APHP-Sorbonne Universit\u00e9, Centre de R\u00e9f\u00e9rence Maladies Neuromusculaires Nord\/Est\/Ile de France, Institut de Myologie, GH Piti\u00e9-Salp\u00eatri\u00e8re , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele","family":"Bonne","sequence":"additional","affiliation":[{"name":"APHP-Sorbonne Universit\u00e9, Centre de R\u00e9f\u00e9rence Maladies Neuromusculaires Nord\/Est\/Ile de France, Institut de Myologie, GH Piti\u00e9-Salp\u00eatri\u00e8re , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline A","family":"Sewry","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Inherited Neuromuscular Diseases and Department of Musculoskeletal Histopathology, RJAH Orthopaedic Hospital , Oswestry, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Willis","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Inherited Neuromuscular Diseases and Department of Musculoskeletal Histopathology, RJAH Orthopaedic Hospital , Oswestry, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richa","family":"Kulshrestha","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Inherited Neuromuscular Diseases and Department of Musculoskeletal Histopathology, RJAH Orthopaedic Hospital , Oswestry, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Tasca","sequence":"additional","affiliation":[{"name":"UOC di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Phadke","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Queen Square Institute of Neurology & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer E","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology , London, UK"},{"name":"School of Cancer Sciences, University of Southampton , Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"From the Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health , London, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust , London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"2024032523420751100_nlab088-B1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ncl.2014.05.002","article-title":"Duchenne and Becker muscular dystrophies","volume":"32","author":"Flanigan","year":"2014","journal-title":"Neurol Clin"},{"key":"2024032523420751100_nlab088-B2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","article-title":"Dystrophin and mutations: One gene, several proteins, multiple phenotypes","volume":"2","author":"Muntoni","year":"2003","journal-title":"Lancet Neurol"},{"key":"2024032523420751100_nlab088-B3","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.3390\/ijms19061546","article-title":"Detection of dystrophin Dp71 in human skeletal muscle using an automated capillary western assay system","volume":"19","author":"Kawaguchi","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2024032523420751100_nlab088-B4","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1002\/mus.1192","article-title":"The dystrophin-glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies","volume":"24","author":". 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