Researchers at the National Institutes of Health have discovered that a previously unexplained fatal form of Osteogenesis Imperfecta — a disorder that weakens bones and which may cause frequent fractures — results from a genetic defect in a protein involved in the production of collagen.
The study appears in the December 28 “New England Journal of Medicine”.
The affected gene contains the information for cartilage associated protein, or CRTAP. The function of CRTAP is not well understood, but it is known to be part of a complex of proteins involved in the chemical transformation of collagen from simple protein “chains” into its final form.
The well-known forms of Osteogenesis Imperfecta (OI) result from a defect in the genes for type I collagen, which serves as a kind of molecular scaffolding that holds together bone, tendons, skin and other tissues. The collagen defects result from dominant mutations, requiring only one copy of a mutant gene to cause bone disease. The NIH researchers discovered that mutations in the CRTAP gene accounted for a recessive form of the disorder — requiring two copies of the affected gene to show a particular trait.
The NIH team was led by Joan Marini, M.D., Ph.D., Chief of NIH’s Bone and Extracellular Matrix Branch and was assisted by colleagues at other institutions.