754 TYPE I COLLAGEN SYNTHESIS IN OSTEOGENESIS IMPERFECTA

Abstract

We have examined the collagenous protein synthesized by dermal fibroblasts from 35 patients with osteogenesis imperfecta (OI) and 12 controls. Fibroblasts were incubated with ³H-proline; the total collagenous proteins were determined by collagenase digestion and the ratio of type I to type III collagen estimated by interrupted acrylamide gel electrophoresis. At present, four patterns of type I synthesis have been observed roughly correlating with the clinical phenotypes: 1) Low type I synthesis without an abnormality in migration or ratio of the α₁(I) and α₂ chains. 2) Low or normal type I synthesis with an abnormality in the α₁/α₂ ratio or a structural abnormality of the α₂ chains. Patients in either group have dominantly or sporadically inherited OI which is mildly to moderately deforming. 3) Normal to elevated type I synthesis with a normal type III to type I ratio. Both the α₁(I) and α₂ chains show delayed migration. These patients belong to the progressively deforming group as described by Sillence since they have severe growth retardation and are uniformly wheelchair bound. 4) Low to normal type I synthesis with structural abnormalities in the α₁(I) chain. The α₁(I) chain findings have only been found in patients with the neonatal lethal form of OI. The results of this biochemical survey indicate that a wide range of identifiable abnormalities of type I collagen are present in most patients with OI reflecting the genetic heterogeneity of this disease.

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