Deficiency of Cartilage-Associated Protein in Recessive Lethal Osteogenesis Imperfecta

Mutations in type I collagen cause classic osteogenesis imperfecta, an autosomal dominant disease; however, a recessive form has long been suspected. The authors showed that deficiency in the cartilage-associated protein, required for the post-translational prolyl 3-hydroxylation of collagen, was associated with autosomal recessive osteogenesis imperfecta in three infants who did not have a primary collagen defect. These data suggest that prolyl 3-hydroxylation of type I collagen is important for bone formation. The authors show that deficiency in the cartilage-associated protein was associated with autosomal recessive osteogenesis imperfecta in three infants who did not have a primary collagen defect. Osteogenesis imperfecta, or “brittle bone disease,” is an autosomal dominant genetic disorder characterized by bone fragility with susceptibility to fracture. 1 The clinical range of osteogenesis imperfecta (types I through IV) 2 extends from mild symptoms to a perinatal lethal condition (Table 1 of the Supplementary Appendix, available with the full text of this article at www.nejm.org). Mutations in type I collagen, the major structural protein of bone and skin, cause most cases of osteogenesis imperfecta. 3 Type I collagen is a heterotrimer, composed of two α1(I) and one α2(I) chains. Both α chains have a primary structure of uninterrupted repeats of the tripeptide . . .