Understanding the causes of inherited lymphoedema

Functional analysis of GATA2 and KIF11; newly identified genes for primary lymphoedema

As well as the circulatory system that transports blood around the body, we also have a second circulatory system called the lymphatic system. It is made up of a network of vessels carrying ‘lymph’ fluid containing protein, fats, water and waste from cells away from tissues to glands called lymph nodes, which contain numerous immune cells to trap foreign particles, and return the filtered fluid to the blood. Lymphoedema is a condition that occurs when the lymphatic system becomes damaged or disrupted – lymph fluid cannot be drained from the tissues, causing swelling. It usually affects the arms or legs, which are then prone to infection and scarring. Primary lymphoedema develops at birth or shortly after puberty and is caused by faulty genes. Scientists studying inherited lymphoedema have found that altered lymphatic genes frequently have consequences to the heart and circulatory system, such as congenital heart disease and the failure of valves in blood vessels. Understanding what these faulty genes do may therefore reveal clues about cardiovascular disease. BHF funding has enabled Dr Pia Ostergaard and colleagues at St George’s, University of London, to discover three new genes - GJC2, GATA2 and KIF11 - that when altered, lead to lymphoedema. They have now been awarded a new BHF grant to investigate what these genes do in the lymphatic system and if they are involved in the formation of new lymph vessels. They will use both cultured cells and mouse models to find out how these genetic changes lead to lymphatic disease in people. This research will enable us to better understand the causes of genetic lymphoedema and may reveal new clues about heart disease.