Collection of clinical material from patients with familial and/or isolated primary lymphedema, lymphatic malformation and/or associated phenotype. Mutational profiling of such samples for the already known genes. Definition of novel positional and functional candidate genes, and their screening for disease causative/ associated mutations. Expression of selected identified (mutated) protein products and eventual cloning of mouse homologues for in vivo studies. Validation of novel angiogenic genes using morpholino knockdowns in zebrafish. Preparatory experiments for the QTL analysis to identify novel lymphangiogenic genes. Generation of reporter ES cells (to generate reporter mice). Allele dosage-dependent lymphedema phenotypes.