PITTSBURGH, June 29 -- Clinicians have long puzzled over families whose members have limbs swollen with lymphatic fluid. Now, University of Pittsburgh investigators and their collaborators from the University of Helsinki have pinpointed genetic errors that account for this disease, hereditary lymphedema. The mutations, described in the June issue of Nature Genetics, occur in the gene for vascular endothelial growth factor receptor (VEGFR3). This cell receptor is critical for the growth of lymph vessels that are responsible for draining tissues of extracellular fluid. This new information should enable genetic testing, in addition to providing a therapeutic target for inherited forms of lymphedema and for lymphedema that arises from injury, surgery or infection.
"Our work is the first to identify a genetic mutation responsible for lymphedema," stated David Finegold, M.D., associate professor of human genetics at the University of Pittsburgh's Graduate School of Public Health (GSPH). "This work provides a foundation for understanding a biological mechanism causal for hereditary lymphedema and crucial for the normal development of lymph vessels."
Lymphedema affects as many as 175 million people worldwide. Hereditary lymphedema arises spontaneously in individuals who have the genetic mutation. Secondary lymphedema may result from infection, injury or common surgical procedures such as those for cancer in which lymph nodes are removed. Lymphedema can lead to infection, pain, severe disability or sometimes cancer. Current treatments involve applying pressure to drain the lymph fluid.
An intricate series of fine tubes and nodes stretching throughout the body, the lymph system performs the mundane but critical task of mopping up excess fluid as well as molecules and cells that stray from nearby blood vessels.
As with other organs, development of the lymph system is tightly regulated. One protein involved in the process is VEGF-C, which binds to
Contact: Lauren Ward
University of Pittsburgh Medical Center