Journal of Biological Chemistry
Volume 277, Issue 46, 15 November 2002, Pages 43557-43564
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GLYCOBIOLOGY AND EXTRACELLULAR MATRICES
Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2Mutations in Two Families with Ullrich Congenital Muscular Dystrophy*

https://doi.org/10.1074/jbc.M207696200Get rights and content
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We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of theCOL6A2 gene, in patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers of one mutant allele, are unaffected, although heterozygous mutations in collagen VI caused Bethlem myopathy. Here we investigated the consequences of threeCOL6A2mutations in fibroblasts from patients and their parents in two Ullrich families. All three mutations lead to nonsense-mediated mRNA decay. However, very low levels of undegraded mutant mRNA remained in patient B with compound heterozygous mutations at the distal part of the triple-helical domain, resulting in deposition of abnormal microfibrils that cannot form extensive networks. This observation suggests that the C-terminal globular domain is not essential for triple-helix formation but is critical for microfibrillar assembly. In all parents, theCOL6A2 mRNA levels are reduced to 57–73% of the control, but long term collagen VI matrix depositions are comparable with that of the control. The almost complete absence of abnormal protein and near-normal accumulation of microfibrils in the parents may account for their lack of myopathic symptoms.

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Published, JBC Papers in Press, September 5, 2002, DOI 10.1074/jbc.M207696200

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This work was supported by National Institutes of Health Grant AR38912 (to M.-L. C.), European Union Grant QLG1–1999-00870 (to E. B., P. S., S. S., and G. P.), French Telethon (to G. P.), and Ministero della Salute Grant PF 83/2001 (to P. S. and S. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.