1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent α1(III) and α1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the α1(I) to α2 chains of type I collagen has also been measured.
2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio α1 (III)/α1 (I) was significantly increased (P < 0.001) and the ratio α1(I)/α2 significantly decreased (P < 0.005) compared with age-matched control subjects.
3. In three infants with lethal (type II) osteogenesis imperfecta the ratio α1(III)/α1 (I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients.
4. The ratio of α1(I)/α2 and of α1(III)/α2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio α1(III)/α1 (I) was increased.
5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied.
6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the α1(I) chain rather than of the α2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.