Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
Address for correspondence: Robert E. Ferrell, Ph.D., Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
rferrell{at}mail.hgen.pitt.edu
Ann. N.Y. Acad. Sci. 979: 39-51 (2002).
The hereditary lymphedemas provide an opportunity to identify
genes involved in normal and deranged lymphatic development.
Genetic analysis of families with Milroy's disease identified
mutations in VEGFR3 as a cause of congenital lymphedema, confirming
the importance of VEGFC/VEGFR3 signaling in lymphatic development.
These observations led to the identification of a mouse model
for primary lymphedema, and subsequent analysis of this mouse
model, using transgenic and gene transfer techniques, has provided
initial clues to the development of a biologically based therapy
for primary lymphedema. Of more importance from a public health
perspective is the fact that manipulation of this pathway may
lead to effective therapies for the more prevalent forms of
secondary lymphedema. Identification of FOXC2 as the gene mutated
in the lymphedema-distichiasis syndrome has revealed new molecular
insight into lymphatic development. Molecular analysis of the
FOXC2 pathway may provide clues to developmental pathways shared
by the lymphatic system and the other developmental abnormalities
associated with this complex syndrome. With improving knowledge
of the human genome, genetic analysis of families with lymphedema
continues to offer one of the most promising approaches to identifying
genes influencing lymphatic development.
