{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:28:24Z","timestamp":1784910504122,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","award":["Ricerca Corrente 2023"],"award-info":[{"award-number":["Ricerca Corrente 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Collagen VI is a heterotrimeric protein expressed in several tissues and involved in the maintenance of cell integrity. It localizes at the cell surface, creating a microfilamentous network that links the cytoskeleton to the extracellular matrix. The heterotrimer consists of three chains encoded by COL6A1, COL6A2 and COL6A3 genes. Recessive and dominant molecular defects cause two main disorders, the severe Ullrich congenital muscular dystrophy and the relatively mild and slowly progressive Bethlem myopathy. We analyzed the clinical aspects, pathological features and mutational spectrum of 15 COL6-mutated patients belonging to our cohort of muscular dystrophy probands. Patients presented a heterogeneous phenotype ranging from severe forms to mild adult-onset presentations. Molecular analysis by NGS detected 14 different pathogenic variants, three of them so far unreported. Two changes, localized in the triple-helical domain of COL6A1, were associated with a more severe phenotype. Histological, immunological and ultrastructural techniques were employed for the validation of the genetic variants; they documented the high variability in COL6 distribution and the extracellular matrix disorganization, highlighting the clinical heterogeneity of our cohort. The combined use of these different technologies is pivotal in the diagnosis of COL6 patients.<\/jats:p>","DOI":"10.3390\/ijms24065551","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T06:57:11Z","timestamp":1678777031000},"page":"5551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Extracellular Matrix Disorganization and Sarcolemmal Alterations in COL6-Related Myopathy Patients with New Variants of COL6 Genes"],"prefix":"10.3390","volume":"24","author":[{"given":"Simona","family":"Zanotti","sequence":"first","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Magri","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neuroscience Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Salani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neuroscience Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Napoli","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9293-6823","authenticated-orcid":false,"given":"Michela","family":"Ripolone","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Ciscato","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Velardo","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"IRCCS Eugenio Medea, Bosisio Parini, 23842 Lecco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gualandi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina di Precisione, \u201cLuigi Vanvitelli\u201d University of Campania and Telethon Institute of Genetics and Medicine (TIGEM), 81100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Sciacco","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Neurology Unit, Department of Neuroscience Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neuroscience Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1383-5248","authenticated-orcid":false,"given":"Giacomo Pietro","family":"Comi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Piga","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neuroscience Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0022-2836(03)00585-0","article-title":"The Supramolecular Organization of Collagen VI Microfibrils","volume":"330","author":"Baldock","year":"2003","journal-title":"J. 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