New brittle bone disease gene identified

Research published last week in the journal Cell has identified a genetic mutation which can lead to osteogenesis imperfecta (OI), a condition which makes bones much more brittle and likely to break.

Previously, most cases of OI were attributed to a mutation in a particular collagen protein which is involved in the formation of collagen fibres, the protein framework on which bone and cartilage are built. Mutations in this protein are dominant and often spontaneous, (not inherited from parents). To make functional collagen fibres, collagen protein undergoes several biochemical modifications immediately after being made. The newly discovered mutation, which is responsible for up to 15 per cent of cases, prevents collagen proteins from being properly modified after they are produced.

In the study carried out by Brendan Boyce at the Centre for Musculoskeletal Research at the University of Rochester Medical Centre, mice were genetically altered so that they lacked the protein involved in collagen formation, called CRTAP (cartilage-associated protein). Examination of the mice revealed they were unable to properly line up the fibres that make up collagen. Collaborative studies at the McGill University in Montreal identified human patients who had OI due to mutations in CRTAP, showing that it has an essential function in humans. The newly discovered mutation is a recessive trait which can be passed down to subsequent generations.

Brendan Lee of the Baylor Collage of Medicine, who led the study, showed that partial loss of CRTAP function protein caused a mild form of the disease, whereas total loss caused a more severe form of the disease. Boyce said 'The study is important because it clarifies a new mechanism by which OI can occur and makes possible new tests to identify affected children and provide them with added medical support'.