A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations

Ullrich congenital muscular dystrophy (UCMD) is caused by recessive and dominant mutations in COL6A genes. We have analysed collagen VI expression in 14 UCMD patients. Sequencing of COL6A genes had identified homozygous and heterozygous mutations in 12 cases. Analysis of collagen VI in fibroblast cultures derived from eight of these patients showed reduced extracellular deposition in all cases and intracellular collagen VI staining in seven cases. This was observed even in cases that showed normal collagen VI labelling in skin biopsies. Collagen VI immunolabelling was reduced in all the available muscle biopsies. When comparisons were possible no correlation was seen between the extent of the reduction in the muscle and fibroblast cultures, the mode of inheritance or the severity of the clinical phenotype. Mutations affecting glycine substitutions in the conserved triple helical domain were common and all resulted in reduced collagen VI. This study expands the spectrum of collagen VI defects and shows that analysis of skin fibroblasts may be a useful technique for the detection of collagen VI abnormalities. In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect.