{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:20:36Z","timestamp":1784874036300,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Collagen type VI-related dystrophies (COL6-RD) are rare diseases with a wide phenotypic spectrum ranging from severe Ullrich\u2019s congenital muscular dystrophy Ullrich congenital muscular dystrophy to much milder Bethlem myopathy Both dominant and recessive forms of COL6-RD are caused by pathogenic variants in three collagen VI genes (<jats:italic>COL6A1<\/jats:italic>, <jats:italic>COL6A2<\/jats:italic> and <jats:italic>COL6A3<\/jats:italic>). The prognosis of these diseases is variable and difficult to predict during early disease stages, especially since the genotype-phenotype correlation is not always clear. For this reason, studies with long-term follow-up of patients with genetically confirmed COL6-RD are still needed. In this study, we present phenotypic and genetic data from 25 patients (22 families) diagnosed with COL6-RD and followed at a single French center, in both adult and pediatric neurology departments. We describe three novel pathogenic variants and identify <jats:italic>COL6A2<\/jats:italic>:c.1970-9G&amp;gt;A as the most frequent variant in our series (29%). We also observe an accelerated progression of the disease in a subgroup of patients. This large series of rare disease patients provides essential information on phenotypic variability of COL6-RD patients as well as on frequency of pathogenic <jats:italic>COL6A<\/jats:italic> gene variants in Southern France, thus contributing to the phenotypic and genetic description of Collagen type VI-related dystrophies.<\/jats:p>","DOI":"10.3389\/fgene.2023.1242277","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:50:29Z","timestamp":1702443029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Retrospective clinical and genetic analysis of COL6-RD patients with a long-term follow-up at a single French center"],"prefix":"10.3389","volume":"14","author":[{"given":"Victor","family":"Morel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Audic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Tardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Verschueren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Salort-Campana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Krahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Chabrol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Gorokhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e124403","DOI":"10.1172\/jci.insight.124403","article-title":"A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies","volume":"4","author":"Bolduc","year":"2019","journal-title":"JCI Insight"},{"key":"B2","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/nrneurol.2011.81","article-title":"The collagen VI-related myopathies: muscle meets its matrix","volume":"7","author":"B\u00f6nnemann","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1002\/ana.22087","article-title":"Early onset collagen VI myopathies: genetic and clinical correlations","volume":"68","author":"Bri\u00f1as","year":"2010","journal-title":"Ann. Neurology"},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.cca.2020.05.011","article-title":"Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) leads to Bethlem myopathy","volume":"508","author":"Choi","year":"2020","journal-title":"Clin. Chimica Acta; Int. J. Clin. Chem."},{"key":"B6","doi-asserted-by":"publisher","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":"B7","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.nmd.2010.04.009","article-title":"Differentiating Emery-Dreifuss muscular dystrophy and collagen VI-related myopathies using a specific CT scanner pattern","volume":"20","author":"Deconinck","year":"2010","journal-title":"Neuromuscul. Disord. NMD"},{"key":"B8","doi-asserted-by":"publisher","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. Neurology, Neurosurg. Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","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. Neurology"},{"key":"B10","article-title":"Collagen VI-related dystrophies","volume-title":"GeneReviews","author":"Foley","year":"2021"},{"key":"B11","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3390\/genes11050539","article-title":"Targeted next-generation sequencing in a large cohort of genetically undiagnosed patients with neuromuscular disorders in Spain","volume":"11","author":"Gonzalez-Quereda","year":"2020","journal-title":"Genes"},{"key":"B12","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41431-018-0305-1","article-title":"A National French consensus on gene lists for the diagnosis of myopathies using next-generation sequencing","volume":"27","author":"Krahn","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"B13","doi-asserted-by":"publisher","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. NMD"},{"key":"B14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.matbio.2017.12.008","article-title":"Collagen VI disorders: insights on form and function in the extracellular matrix and beyond","volume":"71","author":"Lamand\u00e9","year":"2018","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1212\/01.WNL.0000163990.00057.66","article-title":"Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy","volume":"64","author":"Lucioli","year":"2005","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"E662","DOI":"10.1002\/humu.21022","article-title":"Identification and characterization of novel collagen VI non-canonical splicing mutations causing Ullrich congenital muscular dystrophy","volume":"30","author":"Martoni","year":"2009","journal-title":"Hum. Mutat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.nmd.2005.01.004","article-title":"Muscle MRI in Ullrich congenital muscular dystrophy and Bethlem myopathy","volume":"15","author":"Mercuri","year":"2005","journal-title":"Neuromuscul. Disord."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1002\/acn3.649","article-title":"Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients","volume":"5","author":"Nallamilli","year":"2018","journal-title":"Ann. Clin. Transl. Neurology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1413","DOI":"10.1212\/WNL.0000000000011499","article-title":"Association of initial maximal motor ability with long-term functional outcome in patients with COL6-related dystrophies","volume":"96","author":"Natera-de Benito","year":"2021","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3389\/fneur.2018.00147","article-title":"Myopathy with SQSTM1 and TIA1 variants: clinical and pathological features","volume":"9","author":"Niu","year":"2018","journal-title":"Front. Neurology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/ana.21439","article-title":"Collagen VI glycine mutations: perturbed assembly and a spectrum of clinical severity","volume":"64","author":"Pace","year":"2008","journal-title":"Ann. Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.nmd.2013.11.002","article-title":"Diaphragmatic dysfunction in Collagen VI myopathies","volume":"24","author":"Quijano-Roy","year":"2014","journal-title":"Neuromuscul. Disord. NMD"},{"key":"B23","doi-asserted-by":"publisher","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. NMD"},{"key":"B24","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/cge.12839","article-title":"Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic","volume":"91","author":"Stehl\u00edkov\u00e1","year":"2017","journal-title":"Clin. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1038\/s41436-020-0840-3","article-title":"Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness","volume":"22","author":"T\u00f6pf","year":"2020","journal-title":"Genet. Med. Official J. Am. Coll. Med. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3233\/JND-200577","article-title":"Clinical and molecular spectrum associated with COL6A3 c.7447A>G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies","volume":"8","author":"Villar-Quiles","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"B27","doi-asserted-by":"publisher","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. Neurology Neurosurg."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1242277\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:50:32Z","timestamp":1702443032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1242277\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,13]]},"references-count":27,"alternative-id":["10.3389\/fgene.2023.1242277"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1242277","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,13]]},"article-number":"1242277"}}