{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:09:34Z","timestamp":1780927774588,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,9,20]],"date-time":"2007-09-20T00:00:00Z","timestamp":1190246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of \u03b11(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of <jats:italic>COL6A1<\/jats:italic> exon 14, and three patients had novel mutations leading to in\u2010frame deletions toward the N\u2010terminal end of the triple\u2010helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A\u2010domains of <jats:italic>COL6A2<\/jats:italic> and <jats:italic>COL6A3.<\/jats:italic> Collagen VI intracellular and extracellular assembly was normal in one of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A\u2010domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle. Ann Neurol 2007<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21213","type":"journal-article","created":{"date-parts":[[2007,9,20]],"date-time":"2007-09-20T21:19:10Z","timestamp":1190323150000},"page":"390-405","source":"Crossref","is-referenced-by-count":62,"title":["Molecular consequences of dominant Bethlem myopathy collagen VI mutations"],"prefix":"10.1002","volume":"62","author":[{"given":"Naomi L.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishika A.","family":"Pace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Peat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi E.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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