Brouillard P, Boon L, Vikkula M, et al.
The Journal of clinical investigation. Date of publication 2014 Mar 1;volume 124(3):898-904.
1. J Clin Invest. 2014 Mar;124(3):898-904. doi: 10.1172/JCI71614. Epub 2014 Mar 3.
Genetics of lymphatic anomalies.
Brouillard P, Boon L, Vikkula M.
Lymphatic anomalies include a variety of developmental and/or functional defects
affecting the lymphatic vessels: sporadic and familial forms of primary
lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic
malformations, and overgrowth syndromes with a lymphatic component. Germline
mutations have been identified in at least 20 genes that encode proteins acting
around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors.
These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways
and explain more than a quarter of the incidence of primary lymphedema, mostly of
inherited forms. More common forms may also result from multigenic effects or
post-zygotic mutations. Most of the corresponding murine knockouts are homozygous
lethal, while heterozygotes are healthy, which suggests differences in human and
murine physiology and the influence of other factors.
DOI: 10.1172/JCI71614
PMCID: PMC3938256
PMID: 24590274 [Indexed for MEDLINE]
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