Production of overmodified type I procollagen in a case of osteogenesis imperfecta

Collagen synthesis in cultured skin fibroblasts from a patient with osteogenesis imperfecta was studied. Approximately 2 fold accumulation of collagen in the cell layer was found. The slower mobility of proα₁ (I) and proα₂ (I) as well as α₁ and α₂ (I) polypeptide on sodium dodecylsulfate-polyacrylamide gel electrophoresis was detected, indicating that abnormal posttranslational modification could be present in type I procollagen in patient fibroblasts. The degrees of hydroxylation and subsequent glycosylation of lysine residues in the affected collagen were elevated 1.5 and 1.4 fold, respectively. There were no significant changes in the relative content of type III to type I collagen nor the incorporation of mannose into the carboxyterminal propeptide of proα₁ (I) and proα₂ (I). These results indicate that the patient produces an over-modified type I procollagen which is responsible for the clinical features and has a collagen abnormality already reported in type II osteogenesis imperfecta.