Classic osteogenesis imperfecta, an autosomal dominant disorder associated with 
osteoporosis and bone fragility, is caused by mutations in the genes for type I 
collagen. A recessive form of the disorder has long been suspected. Since the 
loss of cartilage-associated protein (CRTAP), which is required for 
post-translational prolyl 3-hydroxylation of collagen, causes severe 
osteoporosis in mice, we investigated whether CRTAP deficiency is associated 
with recessive osteogenesis imperfecta. Three of 10 children with lethal or 
severe osteogenesis imperfecta, who did not have a primary collagen defect yet 
had excess post-translational modification of collagen, were found to have a 
recessive condition resulting in CRTAP deficiency, suggesting that prolyl 
3-hydroxylation of type I collagen is important for bone formation.