Investigating mutations that cause Bethlem myopathy and Ullrich congenital muscular dystrophy

Prof Kate Bushby

Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD) can both be caused by mutations in the gene coding for the collagen VI protein. BM is a relatively mild condition and is characterised by weakness in the proximal muscles – that is the limb muscles that are closer to the trunk of the body such as upper arms or thighs. BM also causes joint contractures (loss of motion in the joints) in the elbows, ankles and fingers. Ullrich CMD, however, tends to cause severe muscle weakness with an early onset. It can be associated with respiratory problems, proximal joint contractures and double jointedness of the hands and feet.

It has been known for some time that mutations in the gene coding for collagen VI could cause BM or UCMD. Collagen VI is a protein that forms part of an important structural layer found on the outside of the muscle cells. However, a proportion of people who are thought to have BM and UCMD do not appear to have a mutation in the collagen VI gene. This suggests that there could be other genes that are affected in BM and UCMD. Prof Bushby will be studying the DNA from patients with BM or UCMD but in whom there appears to be no mutation in collagen VI. They will investigate several candidate genes in the hopes of identifying new mutations that could be causing the disease. These candidates are chosen based on the function of the protein they produce, for example proteins with similar functions to collagen VI. In addition they will be studying the DNA from several large families with BM and UCMD as a second approach to identifying new genes and mutations that could be involved.

Understanding the exact nature of disease-causing mutations not only allows clinicians to give patients an exact genetic diagnosis but can also be important in the development of therapies.

Project leader: Prof. Kate Bushby
Location: University of Newcastle upon Tyne
Duration of project: 2 years (starting October 2008)
Total project cost: £95,485
Official project title: Identifying novel molecular pathways and therapeutic targets for Bethlem myopathy and Ullrich congenital muscular dystrophy

It is only through your contributions that we can continue to fund the vital work that takes us closer to finding treatments and cures for muscle disease. Donate now and help change the lives of thousands of people living with muscle disease. Thank you for your support.

Keep in touch