{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:32:08Z","timestamp":1785321128304,"version":"3.55.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2021,7,30]]},"abstract":"\n Background:<\/jats:title>\n Dominant and recessive autosomal pathogenic variants in the three major genes ( COL6A1-A2-A3) encoding the extracellular matrix protein collagen VI underlie a group of myopathies ranging from early-onset severe conditions (Ullrich congenital muscular dystrophy) to milder forms maintaining independent ambulation (Bethlem myopathy). Diagnosis is based on the combination of clinical presentation, muscle MRI, muscle biopsy, analysis of collagen VI secretion, and COL6A1-A2-A3 genetic analysis, the interpretation of which can be challenging.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n To refine the phenotypical spectrum associated with the frequent COL6A3 missense variant c.7447A>G (p.Lys2483Glu).<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n We report the clinical and molecular findings in 16 patients: 12 patients carrying this variant in compound heterozygosity with another COL6A3 variant, and four homozygous patients.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Patients carrying this variant in compound heterozygosity with a truncating COL6A3 variant exhibit a phenotype consistent with COL6-related myopathies (COL6-RM), with joint contractures, proximal weakness and skin abnormalities. All remain ambulant in adulthood and only three have mild respiratory involvement. Most show typical muscle MRI findings. In five patients, reduced collagen VI secretion was observed in skin fibroblasts cultures. All tested parents were unaffected heterozygous carriers. Conversely, two out of four homozygous patients did not present with the classical COL6-RM clinical and imaging findings. Collagen VI immunolabelling on cultured fibroblasts revealed rather normal secretion in one and reduced secretion in another. Muscle biopsy from one homozygous patient showed myofibrillar disorganization and rimmed vacuoles.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n In light of our results, we postulate that the COL6A3 variant c.7447A>G may act as a modulator of the clinical phenotype. Thus, in patients with a typical COL6-RM phenotype, a second variant must be thoroughly searched for, while for patients with atypical phenotypes further investigations should be conducted to exclude alternative causes. This works expands the clinical and molecular spectrum of COLVI-related myopathies.<\/jats:p>\n <\/jats:sec>","DOI":"10.3233\/jnd-200577","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T14:22:26Z","timestamp":1615904546000},"page":"633-645","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Clinical and Molecular Spectrum Associated with\n COL6A3<\/i>\n c.7447A>G p.(Lys2483Glu) Variant: Elucidating its Role in Collagen VI-related Myopathies"],"prefix":"10.1177","volume":"8","author":[{"given":"Roc\u00edo N.","family":"Villar-Quiles","sequence":"first","affiliation":[{"name":"AP-HP, Reference Center for Neuromuscular Disorders, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris, France"},{"name":"Centre de Recherche en Myologie, Institut de Myologie, Sorbonne Universit\u00e9, Inserm, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Donkervoort","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"de Becdeli\u00e8vre","sequence":"additional","affiliation":[{"name":"AP-HP, D\u00e9partement de G\u00e9n\u00e9tique, H\u00f4pital Henri Mondor, Cr\u00e9teil, France"},{"name":"AP-HP, Centre de G\u00e9n\u00e9tique Mol\u00e9culaire et Chromosomique, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, GH Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine","family":"Gartioux","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Sorbonne Universit\u00e9, Inserm, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Jobic","sequence":"additional","affiliation":[{"name":"AP-HP, Centre de G\u00e9n\u00e9tique Mol\u00e9culaire et Chromosomique, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, GH Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Reghan","family":"Foley","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley M.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 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