A defect in the structure of type I procollagen in a patient who had osteogenesis imperfecta: excess mannose in the COOH-terminal propeptide.
Fibroblasts from normal human subjects and from a patient who had osteogenesis imperfecta were incubated with [3H]mannose, and types I and III procollagens were isolated from the culture medium. The type I procollagen from the patient's fibroblasts contained 2-3 time more [3H]mannose than the type I procollagen from the normal fibroblasts. In contrast, there was no difference in the [3H]mannose content of the type III procollagen simultaneously synthesized and secreted by the same cells. Isolation of a collagenase-resistant peptide fragment from the type I procollagen showed that the excess mannose was located in the COOH-terminal propeptide of the protein. Radioimmunoassays of the medium and the cell layer showed that the type I procollagen synthesized by the patient's fibroblasts was secreted into the medium more slowly than the type I procollagen synthesized by normal fibroblasts. These results appear to provide evidence for an alteration in the structure of procollagen in osteogenesis imperfecta.
D002478:Cells, Cultured; D003470:Culture Media; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008358:Mannose / Q000378:metabolism; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D006023:Glycoproteins; D011347:Procollagen; D008358:Mannose