Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

摘要: We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers one mutant allele, unaffected, although heterozygous VI caused Bethlem myopathy. Here we investigated consequences three fibroblasts and their parents two families. All lead to nonsense-mediated mRNA decay. However, very low levels undegraded remained patient B compound at distal part triple-helical domain, deposition abnormal microfibrils that cannot form extensive networks. This observation suggests C-terminal globular domain is not essential for triple-helix formation but critical microfibrillar assembly. In reduced 57-73% control, long term matrix depositions comparable control. The almost complete absence protein near-normal accumulation may account lack myopathic symptoms.