Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.

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Abstract
Osteogenesis imperfecta is a clinically and genetically heterogeneous group of inherited connective tissue disorders in which bone fragility is the predominant feature. Cultured dermal fibroblasts from 1 patient with the lethal perinatal form of osteogenesis imperfecta secrete type I procollagen at a rate half that of normal cells. Short-term labeling experiments and treatment with .alpha.,.alpha.''-dipyridyl (which prevents posttranslational prolyl and lysyl hydroxylation) demonstrated that these cells produce 2 distinct pro.alpha.1(I) chains, which are synthesized at the same rate. Analysis of CNBr peptides indicated that the 2 chains differ in their primary structures. Structural abnormalities in type I procollagen prevent this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. While the lethal perinatal form of osteogenesis imperfecta may be heterogeneous, the underlying pathogenesis of at least 1 form may be decreased secretion of type I procollagen.