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Previous Volume 355:2757-2764 December 28, 2006 Number 26 Next

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SUMMARY

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.

Source Information

From the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (A.M.B., W.C., W.A.C., S.L., E.M., N.K., T.E.U., A.A., A.W.F., J.C.M.); Baylor College of Medicine, Houston (R.M., B.L.); the Orthopaedic Research Laboratories, University of Washington, Seattle (M.W., D.R.E.); the University of Oklahoma Health Sciences Center, Oklahoma City (J.J.M., P.L.W.); and the Medical College of Virginia, Richmond (U.T.S.).

Ms. Barnes and Drs. Chang and Morello contributed equally to this article.

Address reprint requests to Dr. Marini at the Bone and Extracellular Matrix Branch, NICHD, NIH, Bldg. 10, Rm. 10N260, 9000 Rockville Pike, Bethesda, MD 20892, or at oidoc{at}helix.nih.gov.

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