Gene Mutation Linked to Lymphatic Dysfunction Identified

A genetic mutation for inherited lymphedema that affects lymphatic function has been discovered by researchers at the University of Pittsburgh Graduate School of Public Health. Findings will be reported in the June issue of the American Journal of Human Genetics.

Lymphedema is the swelling of body tissues caused by an accumulation of fluid in a blocked or damaged lymphatic system. “Lymphedema was first described hundreds of years ago, and yet it remains a very poorly understood disease,” notes David N. Finegold, M.D., co-principal investigator of the study and professor of human genetics, University of Pittsburgh Graduate School of Public Health. Previous work identified six genes linked to the development of lymphedema, but until now researchers had no insight into the genetic factors responsible for lymphatic vascular abnormalities.

Dr. Finegold’s research was based on the University of Pittsburgh Lymphedema Family Study, which began collecting data from affected families in 1995 to learn more about the risk factors and causes of inherited, or primary, lymphedema. They sequenced three genes and observed that mutations in one of these genes, GJC2, was found in primary lymphedema families.

They say that these variations are likely to impair the ability of cells to push fluid throughout the lymphatic system by interrupting their signaling. Without proper signaling, cell contraction necessary for the movement of fluid does not occur, leading to its accumulation in soft body tissues.