{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:08:38Z","timestamp":1791896918159,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Euro-NMD Project 101156434","award":["WP4 CPMS"],"award-info":[{"award-number":["WP4 CPMS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Collagen VI is an extracellular matrix component encoded by COL6A1, COL6A2 and COL6A3 genes. Causative variants in these genes are associated with the following collagen VI-related myopathies: severe Ullrich congenital muscular dystrophy (UCMD), milder Bethlem myopathy (BM) and intermediate phenotypes (INT). We report the mutation landscape of COL6A genes in 138 Italian patients affected with a collagen VI-related phenotype. The patient cohort included 44 (32%) UCMD, 9 (7%) INT, 61 (44%) BM and 21 (15%) INT\/BM patients; 3 patients (2%) with a myosclerosis myopathy (MM) phenotype were also considered. We identified 104 different variants: 26 in COL6A1 (25%), 52 in COL6A2 (50%) and 26 in COL6A3 (25%). The variant spectrum includes missense, splicing, small indel, frameshifting and nonsense variants. Glycine substitutions in the triple helical domain of the collagen VI protein are the commonest variants and occur in all phenotypes. Our genetic profiling disclosed a unique mutation scenario and phenotypic association of the COL6A2 gene with respect to COL6A1 and COL6A3, which may be related to a different evolutive history. Landscape mutation analysis of variants occurring in ultrarare conditions, such as collagen VI-related myopathies, is crucial to better understand the variations\u2019 profile and to gain insight into fundamental knowledge about gene structure and its evolutive origin.<\/jats:p>","DOI":"10.3390\/biom15101426","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:06:53Z","timestamp":1759932413000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Landscape Analysis of COL6A1, COL6A2, and COL6A3 Pathogenic Variants in a Large Italian Cohort Presenting with Collagen VI-Related Myopathies: A Nationwide Report"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0232-196X","authenticated-orcid":false,"given":"Fernanda","family":"Fortunato","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1335-7885","authenticated-orcid":false,"given":"Laura","family":"Fiocco","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-1660","authenticated-orcid":false,"given":"Alice","family":"Margutti","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Neri","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Pediatric Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Pediatric Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Ricci","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS A. Gemelli University Polyclinic Foundation, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-5365","authenticated-orcid":false,"given":"Eugenio Maria","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Nemo Clinical Center, IRCCS A. Gemelli University Polyclinic Foundation, 00168 Rome, Italy"},{"name":"Pediatric Neurology, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-6124","authenticated-orcid":false,"given":"Marika","family":"Pane","sequence":"additional","affiliation":[{"name":"Nemo Clinical Center, IRCCS A. Gemelli University Polyclinic Foundation, 00168 Rome, Italy"},{"name":"Pediatric Neurology, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Massa","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular Disorders, Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-5212","authenticated-orcid":false,"given":"Giulia","family":"Greco","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular Disorders, Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-8055","authenticated-orcid":false,"given":"Angela Lucia","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Psychiatry, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9571-0862","authenticated-orcid":false,"given":"Cristina","family":"Cereda","sequence":"additional","affiliation":[{"name":"Center of Functional Genomics and Rare Diseases, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"},{"name":"Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3603-5478","authenticated-orcid":false,"given":"Antonella","family":"Pini","sequence":"additional","affiliation":[{"name":"Pediatric Neuromuscular Unit, IRCCS Institute of Neurological Sciences of Bologna, 40139 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-1198","authenticated-orcid":false,"given":"Luciano","family":"Merlini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Biomedical and Neuromotor Science, DIBINEM, University of Bologna, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-0952","authenticated-orcid":false,"given":"Carlo","family":"Fusco","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-6356","authenticated-orcid":false,"given":"Carmelo","family":"Rodolico","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Messina","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"Child Neuropsichiatry Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy"},{"name":"Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Muscle Disease Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0606-8797","authenticated-orcid":false,"given":"Monica","family":"Traverso","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Moroni","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-7288","authenticated-orcid":false,"given":"Sara","family":"Gibertini","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-4156","authenticated-orcid":false,"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Picillo","sequence":"additional","affiliation":[{"name":"Cardiomyology and Medical Genetics, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0925-7158","authenticated-orcid":false,"given":"Luisa","family":"Politano","sequence":"additional","affiliation":[{"name":"Cardiomyology and Medical Genetics, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Scutifero","sequence":"additional","affiliation":[{"name":"Cardiomyology and Medical Genetics, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-3248","authenticated-orcid":false,"given":"Fabiana","family":"Vercellino","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, SS. Antonio e Biagio e Cesare Arrigo Hospital, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Massaro","sequence":"additional","affiliation":[{"name":"Neurology Unit, Santo Stefano Hospital, 59100 Prato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7512","authenticated-orcid":false,"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"},{"name":"NeMO-Brescia Clinical Center for Neuromuscular Diseases, ASST Spedali Civili, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health-IRCCS, Burlo Garofolo, 34137 Trieste, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2019-612X","authenticated-orcid":false,"given":"Federica","family":"Ricci","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurosciences \u201cRita Levi Montalcini\u201d, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4061-4261","authenticated-orcid":false,"given":"Tiziana Enrica","family":"Mongini","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurosciences \u201cRita Levi Montalcini\u201d, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-0100","authenticated-orcid":false,"given":"Rita","family":"Selvatici","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-9870","authenticated-orcid":false,"given":"Alessandra","family":"Ferlini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-057X","authenticated-orcid":false,"given":"Francesca","family":"Gualandi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Sciences, University of Ferrara and Department of Mother and Child, University Hospital S. Anna Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","unstructured":"Yurchenco, P.D., Birk, D.E., and Mecham, R.P. (1994). Collagen type VI. Extracellular Matrix Assembly and Structure, Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6473","DOI":"10.1016\/S0021-9258(19)39351-2","article-title":"Alternative splicing of the human alpha 2(VI) collagen gene generates multiple mRNA transcripts which predict three protein variants with distinct carboxyl termini","volume":"265","author":"Saitta","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8626","DOI":"10.1016\/S0021-9258(18)93020-6","article-title":"Human alpha 3(VI) collagen gene. Characterization of exons coding for the amino-terminal globular domain and alternative splicing in normal and tumor cells","volume":"266","author":"Stokes","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26522","DOI":"10.1074\/jbc.272.42.26522","article-title":"Type VI collagen anchors endothelial basement membranes by interacting with type IV collagen","volume":"272","author":"Kuo","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1749-6632.1990.tb17917.x","article-title":"The structure of type VI collagen","volume":"580","author":"Chu","year":"1990","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gregory, C.A., Ma, J., and Lomeli, S. (2024). The coordinated activities of collagen VI and XII in maintenance of tissue structure, function and repair: Evidence for a physical interaction. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1376091"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s13023-021-01921-2","article-title":"Causative variant profile of collagen VI-related dystrophy in Japan","volume":"16","author":"Inoue","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1212\/WNL.0000000000001303","article-title":"Prevalence of congenital muscular dystrophy in Italy: A population study","volume":"84","author":"Graziano","year":"2015","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2011.81","article-title":"The collagen VI-related myopathies: Muscle meets its matrix","volume":"7","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1212\/01.wnl.0000327611.01687.5e","article-title":"Autosomal recessive myosclerosis myopathy is a collagen VI disorder","volume":"71","author":"Merlini","year":"2008","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1002\/humu.22429","article-title":"Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and COL6A3 is correlated with severity and mode of inheritance in collagen VI myopathies","volume":"34","author":"Butterfield","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/jmg.2002.002311","article-title":"Collagen VI related muscle disorders","volume":"42","author":"Lampe","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ana.22283","article-title":"Large genomic deletions: A novel cause of Ullrich congenital muscular dystrophy","volume":"69","author":"Foley","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaal5209","DOI":"10.1126\/scitranslmed.aal5209","article-title":"Improving genetic diagnosis in Mendelian disease with transcriptome sequencing","volume":"9","author":"Cummings","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1212\/01.wnl.0000271387.10404.4e","article-title":"Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan","volume":"69","author":"Okada","year":"2007","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/cge.13230","article-title":"Genetic and clinical findings in a Chinese cohort of patients with collagen VI-related myopathies","volume":"93","author":"Fan","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s12031-024-02266-8","article-title":"Clinical and Molecular Profiles of a Cohort of Egyptian Patients with Collagen VI-Related Dystrophy","volume":"74","author":"Rafat","year":"2024","journal-title":"J. Mol. Neurosci."},{"key":"ref_18","first-page":"348","article-title":"Collagen VI disorders: Insights on form and function in the extracellular matrix and beyond","volume":"71\u201372","author":"Bateman","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/humu.20704","article-title":"Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance","volume":"29","author":"Lampe","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.nmd.2010.02.012","article-title":"166th ENMC International Workshop on Collagen type VI-related Myopathies, 22\u201324 May 2009, Naarden, The Netherlands","volume":"20","author":"Allamand","year":"2010","journal-title":"Neuromuscul Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.nmd.2009.09.010","article-title":"Autosomal recessive inheritance of classic Bethlem myopathy","volume":"19","author":"Foley","year":"2009","journal-title":"Neuromuscul. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bovolenta, M., Neri, M., Martoni, E., Urciuolo, A., Sabatelli, P., Fabris, M., Grumati, P., Mercuri, E., Bertini, E., and Merlini, L. (2010). Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies. BMC Med. Genet., 11.","DOI":"10.1186\/1471-2350-11-44"},{"key":"ref_23","unstructured":"(2025, July 11). IGV. Available online: http:\/\/software.broadinstitute.org\/software\/igv\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_25","unstructured":"(2025, July 11). Varsome. Available online: https:\/\/varsome.com\/."},{"key":"ref_26","unstructured":"(2025, July 11). Clinvar, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/."},{"key":"ref_27","unstructured":"(2025, July 11). Franklin. Available online: https:\/\/franklin.genoox.com\/clinical-db\/home."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","article-title":"The Human Gene Mutation Database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine","volume":"133","author":"Stenson","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-94-007-7893-1_12","article-title":"Collagen type VI myopathies","volume":"802","author":"Bushby","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_30","first-page":"e1413","article-title":"Association of Initial Maximal Motor Ability with Long-term Functional Outcome in Patients With COL6-Related Dystrophies","volume":"96","author":"Foley","year":"2021","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.nmd.2023.03.003","article-title":"Collagen VI-related myopathies: Clinical variability, phenotype-genotype correlation and exploratory transcriptome study","volume":"33","author":"Kwong","year":"2023","journal-title":"Neuromuscul. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3988\/jcn.2017.13.4.331","article-title":"Clinical, Pathologic, and Genetic Features of Collagen VI-Related Myopathy in Korea","volume":"13","author":"Lee","year":"2017","journal-title":"J. Clin. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3503253","DOI":"10.1155\/2024\/3503253","article-title":"Clinical, Pathologic, and Genetic Spectrum of Collagen VI-Related Disorder in China-A Retrospective Observational Multicenter Study","volume":"2024","author":"Hu","year":"2024","journal-title":"Hum Mutat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3233\/JND-200476","article-title":"Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene","volume":"8","author":"Bardakov","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.ejpn.2017.07.009","article-title":"Somatic mosaicism represents an underestimated event underlying collagen 6-related disorders","volume":"21","author":"Fattori","year":"2017","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1212\/WNL.0b013e3181aae851","article-title":"Natural history of Ullrich congenital muscular dystrophy","volume":"73","author":"Nadeau","year":"2009","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1097\/BPO.0000000000002283","article-title":"Bethlem Myopathy (Collagen VI-Related Dystrophies): A Retrospective Cohort Study on Musculoskeletal Pathologies and Clinical Course","volume":"43","author":"Silverstein","year":"2023","journal-title":"J. Pediatr. Orthop."},{"key":"ref_38","unstructured":"Foley, A.R., Bolduc, V., Guirguis, F., Donkervoort, S., Hu, Y., Orbach, R., McCarty, R.M., Sarathy, A., Norato, G., and Cummings, B.B. (2024). The recurrent deep intronic pseudoexon-inducing variant COL6A1 c.930+189C>T results in a consistently severe phenotype of COL6-related dystrophy: Towards clinical trial readiness for splice-modulating therapy. medRxiv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.omtn.2020.05.029","article-title":"Exon-Skipping Oligonucleotides Restore Functional Collagen VI by Correcting a Common COL6A1 Mutation in Ullrich CMD","volume":"21","author":"Aguti","year":"2020","journal-title":"Mol. Ther. Nucleic Acids."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43557","DOI":"10.1074\/jbc.M207696200","article-title":"Effects on collagen VI mRNA stability and microfibrillar assembly of three COL6A2 mutations in two families with Ullrich congenital muscular dystrophy","volume":"277","author":"Zhang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105734","DOI":"10.1016\/j.clineuro.2020.105734","article-title":"Clinical features of collagen VI-related dystrophies: A large Brazilian cohort","volume":"192","author":"Zanoteli","year":"2020","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Morel, V., Audic, F., Tardy, C., Verschueren, A., Attarian, S., Nguyen, K., Salort-Campana, E., Krahn, M., Chabrol, B., and Gorokhova, S. (2023). Retrospective clinical and genetic analysis of COL6-RD patients with a long-term follow-up at a single French center. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1242277"},{"key":"ref_43","unstructured":"(2025, July 11). ERN EURO-NMD. Available online: https:\/\/ern-euro-nmd.eu\/."},{"key":"ref_44","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2004). Collagen VI-Related Dystrophies, GeneReviews\u00ae; University of Washington."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Aldharee, H., and Hamdan, H.Z. (2024). Segregation of the COL6A2 Variant (c.1817-3C>G) in a Consanguineous Saudi Family with Bethlem Myopathy. Genes, 15.","DOI":"10.3390\/genes15111405"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4272","DOI":"10.1074\/jbc.M114.632208","article-title":"Aberrant mitochondria in a Bethlem myopathy patient with a homozygous amino acid substitution that destabilizes the collagen VI \u03b12(VI) chain","volume":"290","author":"Zamurs","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1136\/jnnp-2013-307245","article-title":"Bethlem myopathy: Long-term follow-up identifies COL6 mutations predicting severe clinical evolution","volume":"86","author":"Deconinck","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.nmd.2017.06.008","article-title":"Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period","volume":"27","author":"Sframeli","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_49","first-page":"149","article-title":"Severe progressive respiratory involvement requiring ventilator support in autosomal recessive Bethlem myopathy. A case report","volume":"43","author":"Annunziata","year":"2024","journal-title":"Acta Myol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10005","DOI":"10.1074\/jbc.M109.093666","article-title":"Recessive COL6A2 C-globular missense mutations in Ullrich congenital muscular dystrophy: Role of the C2a splice variant","volume":"285","author":"Zhang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/hmg\/ddi025","article-title":"Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy","volume":"14","author":"Baker","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Haq, F., Ahmed, N., and Qasim, M. (2019). Comparative genomic analysis of collagen gene diversity. 3 Biotech, 9.","DOI":"10.1007\/s13205-019-1616-9"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Merlini, L., Sabatelli, P., Gualandi, F., Redivo, E., Di Martino, A., and Faldini, C. (2023). New Clinical and Immunofluoresence Data of Collagen VI-Related Myopathy: A Single Center Cohort of 69 Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512474"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7549","DOI":"10.1038\/s41467-025-62923-3","article-title":"Collagen VI microfibril structure reveals mechanism for molecular assembly and clustering of inherited pathogenic mutations","volume":"16","author":"Godwin","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Fr\u00edas, M., Badosa, C., Jimenez-Mallebrera, C., Porta, J.M., and Rold\u00e1n, M. (2025). The artificial intelligence challenge in rare disease diagnosis: A case study on collagen VI muscular dystrophy. Comput. Biol. Med., 196.","DOI":"10.1016\/j.compbiomed.2025.110610"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13023-023-02776-5","article-title":"Digital health and Clinical Patient Management System (CPMS) platform utility for data sharing of neuromuscular patients: The Italian EURO-NMD experience","volume":"18","author":"Fortunato","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s003359900436","article-title":"Human COL6A1, Genomic characterization of the globular domains structural and evolutionary comparison with COL6A2","volume":"8","author":"Trikka","year":"1997","journal-title":"Mamm. Genome"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T04:33:54Z","timestamp":1760070834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biom15101426"],"URL":"https:\/\/doi.org\/10.3390\/biom15101426","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]}}}