{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:27:11Z","timestamp":1762064831156,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health-Current research IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Limb-girdle muscular dystrophies (LGMD) are clinically and genetically heterogenous presentations displaying predominantly proximal muscle weakness due to the loss of skeletal muscle fibers. Beta-sarcoglycanopathy (LGMDR4) results from biallelic molecular defects in SGCB and features pediatric onset with limb-girdle involvement, often complicated by respiratory and heart dysfunction. Here we describe a patient who presented at the age of 12 years reporting high creatine kinase levels and onset of cramps after strenuous exercise. Instrumental investigations, including a muscle biopsy, pointed towards a diagnosis of beta-sarcoglycanopathy. NGS panel sequencing identified two variants in the SGCB gene, one of which (c.243+1548T&gt;C) was found to promote the inclusion of a pseudoexon between exons 2 and 3 in the SGCB transcript. Interestingly, we detected the same genotype in a previously reported LGMDR4 patient, deceased more than twenty years ago, who had escaped molecular diagnosis so far. After the delivery of morpholino oligomers targeting the pseudoexon in patient-specific induced pluripotent stem cells, we observed the correction of the physiological splicing and partial restoration of protein levels. Our findings prompt the analysis of the c.243+1548T&gt;C variant in suspected LGMDR4 patients, especially those harbouring monoallelic SGCB variants, and provide a further example of the efficacy of antisense technology for the correction of molecular defects resulting in splicing abnormalities.<\/jats:p>","DOI":"10.3390\/ijms23179817","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"9817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antisense Morpholino-Based In Vitro Correction of a Pseudoexon-Generating Variant in the SGCB Gene"],"prefix":"10.3390","volume":"23","author":[{"given":"Francesca","family":"Magri","sequence":"first","affiliation":[{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Zanotti","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Salani","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Ciscato","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2374-194X","authenticated-orcid":false,"given":"Simonetta","family":"Gerevini","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Papa Giovanni XXIII Hospital, 24127 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0932-5173","authenticated-orcid":false,"given":"Lorenzo","family":"Maggi","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Sciacco","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Moggio","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nereo","family":"Bresolin","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo Pietro","family":"Comi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-9816","authenticated-orcid":false,"given":"Dario","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"ref_1","first-page":"207","article-title":"LGMD. 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