{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:05:12Z","timestamp":1760148312418,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["GR-2019-12370504"],"award-info":[{"award-number":["GR-2019-12370504"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Introduction: The Performance of Upper Limb version 2.0 (PUL 2.0) is increasingly used in Duchenne Muscular Dystrophy (DMD) to study longitudinal functional changes of motor upper limb function in ambulant and non-ambulant patients. The aim of this study was to evaluate changes in upper limb functions in patients carrying mutations amenable to skipping exons 44, 45, 51 and 53. Methods: All DMD patients were assessed using the PUL 2.0 for at least 2 years, focusing on 24-month paired visits in those with mutations eligible for skipping exons 44, 45, 51 and 53. Results: 285 paired assessments were available. The mean total PUL 2.0 12-month change was \u22120.67 (2.80), \u22121.15 (3.98), \u22121.46 (3.37) and \u22121.95 (4.04) in patients carrying mutations amenable to skipping exon 44, 45, 51 and 53, respectively. The mean total PUL 2.0 24-month change was \u22121.47 (3.73), \u22122.78 (5.86), \u22122.95 (4.56) and \u22124.53 (6.13) in patients amenable to skipping exon 44, 45, 51 and 53, respectively. The difference in PUL 2.0 mean changes among the type of exon skip class for the total score was not significant at 12 months but was significant at 24 months for the total score (p &lt; 0.001), the shoulder (p = 0.01) and the elbow domain (p &lt; 0.001), with patients amenable to skipping exon 44 having smaller changes compared to those amenable to skipping exon 53. There was no difference within ambulant or non-ambulant cohorts when subdivided by exon skip class for the total and subdomains score (p &gt; 0.05). Conclusions: Our results expand the information on upper limb function changes detected by the PUL 2.0 in a relatively large group of DMD patients with distinct exon-skipping classes. This information can be of help when designing clinical trials or in the interpretation of the real world data including non-ambulant patients.<\/jats:p>","DOI":"10.3390\/children10040746","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Upper Limb Changes in DMD Patients Amenable to Skipping Exons 44, 45, 51 and 53: A 24-Month Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Claudia","family":"Brogna","sequence":"first","affiliation":[{"name":"Pediatric Neurology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marika","family":"Pane","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-5628","authenticated-orcid":false,"given":"Giorgia","family":"Coratti","sequence":"additional","affiliation":[{"name":"Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-2624","authenticated-orcid":false,"given":"Adele","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-4156","authenticated-orcid":false,"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Padua, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-6525","authenticated-orcid":false,"given":"Luca","family":"Bello","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Padua, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Sansone","sequence":"additional","affiliation":[{"name":"The NEMO Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Albamonte","sequence":"additional","affiliation":[{"name":"The NEMO Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-3391","authenticated-orcid":false,"given":"Sonia","family":"Messina","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3603-5478","authenticated-orcid":false,"given":"Antonella","family":"Pini","sequence":"additional","affiliation":[{"name":"Neuromuscular Pediatric Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"NeuroMuscular Unit IRCCS Eugenio Medea, Bosisio Parini, 23842 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Bruno","sequence":"additional","affiliation":[{"name":"Center of Translational and Experimental Myology and Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, IRCCS Istituto Giannina Gaslini and University of Genoa, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Mongini","sequence":"additional","affiliation":[{"name":"Neuromuscular Center, AOU Citt\u00e0 della Salute e della Scienza, University of Torino, 10100 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2019-612X","authenticated-orcid":false,"given":"Federica","family":"Ricci","sequence":"additional","affiliation":[{"name":"Neuromuscular Center, AOU Citt\u00e0 della Salute e della Scienza, University of Torino, 10100 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-8055","authenticated-orcid":false,"given":"Angela","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"National Neurological Institute C. Mondino Foundation, IRCCS, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Battini","sequence":"additional","affiliation":[{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris, 56018 Pisa, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-452X","authenticated-orcid":false,"given":"Riccardo","family":"Masson","sequence":"additional","affiliation":[{"name":"Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0925-7158","authenticated-orcid":false,"given":"Luisa","family":"Politano","sequence":"additional","affiliation":[{"name":"Cardiomiology and Medical Genetics, Department of Experimental Medicine, Universit\u00e0 della Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Italian DMD Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pane, M., Mazzone, E.S., Sivo, S., Sormani, M.P., Messina, S., D\u2019Amico, A., Carlesi, A., Vita, G., Fanelli, L., and Berardinelli, A. (2014). Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108205"},{"key":"ref_2","first-page":"149","article-title":"The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: Considerations for the design of clinical trials","volume":"87","author":"Ricotti","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0140-6736(17)32160-8","article-title":"Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: A prospective cohort study","volume":"391","author":"McDonald","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.nmd.2013.05.006","article-title":"Ambulatory capacity and disease progression as measured by the 6-minute-walk-distance in Duchenne muscular dystrophy subjects on daily corticosteroids","volume":"23","author":"Goemans","year":"2013","journal-title":"Neuromuscul. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Goemans, N., Vanden Hauwe, M., Signorovitch, J., Swallow, E., and Song, J. (2016). Collaborative Trajectory Analysis P. Individualized Prediction of Changes in 6-Minute Walk Distance for Patients with Duchenne Muscular Dystrophy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164684"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1212\/WNL.0b013e318225ab2e","article-title":"Functional changes in Duchenne muscular dystrophy: A 12-month longitudinal cohort study","volume":"77","author":"Mazzone","year":"2011","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3233\/JND-180351","article-title":"Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy","volume":"6","author":"Khan","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"989","DOI":"10.3233\/JND-210643","article-title":"Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial","volume":"8","author":"McDonald","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3233\/JND-150100","article-title":"Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype","volume":"2","author":"Servais","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2270","DOI":"10.1212\/WNL.0000000000009233","article-title":"Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy","volume":"94","author":"Frank","year":"2020","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/nat.2021.0043","article-title":"Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1\/2 Trial","volume":"32","author":"Servais","year":"2022","journal-title":"Nucleic Acid Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3233\/JND-220811","article-title":"Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy","volume":"9","author":"Clemens","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","article-title":"Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial","volume":"77","author":"Clemens","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brogna, C., Coratti, G., Pane, M., Ricotti, V., Messina, S., D\u2019Amico, A., Bruno, C., Vita, G., Berardinelli, A., and Mazzone, E. (2019). Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220714"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Coratti, G., Pane, M., Brogna, C., Ricotti, V., Messina, S., D\u2019Amico, A., Bruno, C., Vita, G., Berardinelli, A., and Mazzone, E. (2021). North Star Ambulatory Assessment changes in ambulant Duchenne boys amenable to skip exons 44, 45, 51, and 53: A 3 year follow up. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253882"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/acn3.51046","article-title":"Genetic modifiers of respiratory function in Duchenne muscular dystrophy","volume":"7","author":"Bello","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/mus.23902","article-title":"The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history observations over 48 weeks from a multicenter study","volume":"48","author":"McDonald","year":"2013","journal-title":"Muscle Nerve"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/dmcn.12213","article-title":"Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy","volume":"55","author":"Mayhew","year":"2013","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pane, M., Coratti, G., Brogna, C., Mazzone, E.S., Mayhew, A., Fanelli, L., Messina, S., D\u2019Amico, A., Catteruccia, M., and Scutifero, M. (2018). Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199223"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.nmd.2019.02.002","article-title":"Respiratory and upper limb function as outcome measures in ambulant and non-ambulant subjects with Duchenne muscular dystrophy: A prospective multicentre study","volume":"29","author":"Ricotti","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1002\/acn3.51417","article-title":"Upper limb disease evolution in exon 53 skipping eligible patients with Duchenne muscular dystrophy","volume":"8","author":"Lilien","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1007\/s00415-022-11133-8","article-title":"Genetic modifiers of upper limb function in Duchenne muscular dystrophy","volume":"269","author":"Sabbatini","year":"2022","journal-title":"J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1212\/WNL.0000000000002891","article-title":"DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study","volume":"87","author":"Bello","year":"2016","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1001\/jamaneurol.2013.4908","article-title":"Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping","volume":"71","author":"Anthony","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/ana.24370","article-title":"Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study","volume":"77","author":"Bello","year":"2015","journal-title":"Ann Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1540","DOI":"10.1212\/WNL.0000000000201626","article-title":"DMD Genotypes and Motor Function in Duchenne Muscular Dystrophy: A Multi-institution Meta-analysis With Implications for Clinical Trials","volume":"100","author":"Muntoni","year":"2023","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2217\/cer-2019-0171","article-title":"Safety and effectiveness of ataluren: Comparison of results from the STRIDE Registry and CINRG DMD Natural History Study","volume":"9","author":"Mercuri","year":"2020","journal-title":"J. Comp. Eff. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1381","DOI":"10.1212\/WNL.0000000000010170","article-title":"Suitability of external controls for drug evaluation in Duchenne muscular dystrophy","volume":"95","author":"Goemans","year":"2020","journal-title":"Neurology"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/4\/746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:12Z","timestamp":1760123952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/4\/746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["children10040746"],"URL":"https:\/\/doi.org\/10.3390\/children10040746","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}