Future research projects

Structural Cardiac Defect

Malformed heart valves and associated aortic aneurysms are found in 1 in 1,000 population. It is possible that these patients also have errors in the Marfan syndrome gene fibrillin-1. Funding is required to study DNA samples from 100 such patients. This could determine how extensive the aortic surgery offered at the first operation should be, preventing multiple heart operations for some of these patients.

The funds raised would provide salary and laboratory consumables for 1 year.

The Role Of TGFBR 2 Gene In Familial Ascending Aortic Aneurysm

We know from our work in the Sonalee laboratory that we have achieved a high yield of mutations using our dHPLC Wave machine to analyse the Marfan syndrome gene. The yield at present is 92%, however 8% of the families refuse to yield their genetic secrets! These families have drawn attention to the fact that there may be other genes involved and the first such gene (TGFBR 2) has been identified by the Marfan research group in Paris, in a large French family. Other Marfan syndrome groups from around the world find that this gene explains approximately 1 in 50 families who have ascending aortic aneurysm, but not classical Marfan syndrome. TGFBR 2 interacts with fibrillin-1, the Marfan gene and so it all makes good sense that this causes aneurysm. We are at present seeking funding to analyse a group of forty families with ascending aortic aneurysm who have not demonstrated mutations in the Marfan gene. A pilot study of 10 such families reveals no TGFBR 2 mutation.

We need to establish what contribution this new gene makes in the UK population.

Preimplantation Genetic Diagnosis

For families with an identified fibrillin-1 mutation, who want to plan to have unaffected children, the most acceptable method is through preimplantation genetic diagnoses (PGD). This is available through most primary care trusts (GPs) on genetic grounds. If the husband has Marfan syndrome, then pregnancy in a normal wife can proceed normally. However if it is the wife who has Marfan syndrome, her cardiac risk may increase in pregnancy, and has to be assessed carefully before hand.

We are at present trying to develop a programme of PGD for Marfan syndrome patients within the UK.