Primary congenital lymphedema (PCL) is the result of a congenital malformation of the lymphatic vasculature and can occur isolated or as part of genetic syndromes. Two genes for primary lymphedema have been identified. The vascular endothelial growth factor receptor VEGFR3/FLT4 is mutated in families with hereditary lymphedema type I (PCL1, OMIM 153100). Mutations in the forkhead transcription factor FOXC2 cause hereditary lymphedema syndromes (PCL2, OMIM 153200) with phenotypic overlap, such as Meige lymphedema, lymphedema-distichiasis syndrome, lymphedema and ptosis, and yellow nail syndrome.

PCL is very heterogeneous and families unlinked to VEGFR3/FLT4 and FOXC2 have been described. The aim of our study is the identification of novel mutations in familial and sporadic cases with PCL. VEGFR3/FLT4 contains 31 exons, two of which are alternatively spliced, and codes for two protein isoforms consisting of 1298 and 1363 amino acid residues, respectively. We have established a mutation screening protocol covering all protein coding exons as well as their respective splicing recognition sites and parts of the 5´ and 3´ untranslated regions of the gene. Mutation screening in more than 15 familial cases revealed several sequence variations, which are currently under more detailed investigation.


Wolfgang Berger (PhD)
István Magyar (PhD)