DEFICIENT EXPRESSION OF THE SMALL PROTEOGLYCAN DECORIN IN A CASE OF SEVERE LETHAL OSTEOGENESIS IMPERFECTA

In osteogenesis imperfecta (OI) the effects of mutations in type I col lagen genes generally reflect their nature and localization, Unrelated individuals sharing identical mutations present, in general, similar clinical phenotypes, However, in some such cases the clinical phenotyp e differs, This variable clinical expression could be the result of ab normalities in other connective tissue proteins, Since decorin is a co mponent of connective tissue, binds to type I collagen fibrils and pla ys a role in matrix assembly, we studied decorin production in skin fi broblasts from OI patients, Cultured fibroblasts from one patient with extremely severe osteogenesis imperfecta (classified as type II/III) who has an alpha 1(I)gly415ser mutation were found to secrete barely d etectable amounts of decorin into culture medium, Western blotting usi ng antibodies raised against decorin confirmed the reduction of the de corin core protein and Northern blot analysis showed decorin mRNA leve ls below the limit of detection. Cells from a patient, with a less sev ere phenotype, bearing a mutation in the same position of the triple h elix (alpha 1(I)gly415) expressed decorin normally, The different clin ical phenotypes could be due to the differing genetic backgrounds of t he patients so it is tempting to conclude that in our most severely af fected patient the absence of decorin aggravates the clinical phenotyp e. (C) 1996 Wiley-Liss, Inc.