Ultrastructural defects of collagen VI filaments in an Ullrich syndrome patient with loss of the alpha3(VI) N10-N7 domains.

Ultrastructural alterations of collagen VI in cultured fibroblasts and reduced collagen VI immunostaining in the papillary dermis and endomysium were detected in a patient with a mild form of Ullrich congenital muscular dystrophy caused by a COL6A3 gene mutation. The patient had been previously demonstrated to express an alpha3(VI) chain shorter than normal due to skipping of the mutated exon. We show that collagen VI filaments are not organized in a normal network in the extracellular matrix secreted by patient's cultured fibroblasts. Moreover, we demonstrate that in this patient the alpha3(VI) chain is produced in lower amounts and it is almost exclusively represented by the shorter, alternatively spliced N6-C5 isoform. These results suggest that different alpha3(VI) chain isoforms, containing also domains of the N10-N7 region, are required for assembling a proper collagen VI network in the extracellular matrix.