Journal Article

Genetics of lymphatic anomalies

Boon, Laurence, Vikkula, Miikka, Brouillard, Pascal

2014

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Animals / Biomedical research / Breast cancer / Care and treatment / Connexins - genetics / Connexins - metabolism / Development and progression / Gene Expression Regulation / Gene mutations / Genetic aspects / Genetic Predisposition to Disease / Genetics / Humans / Kinases / Lymphatic Abnormalities - genetics / Lymphatic diseases / Lymphatic system / Lymphedema - genetics / Lymphedema - metabolism / Mutation / Physiological aspects / ras Proteins - genetics / Review Series / Rodents / Vascular endothelial growth factor / Vascular Endothelial Growth Factor C - genetics / Vascular Endothelial Growth Factor C - metabolism / Vascular Endothelial Growth Factor Receptor-3 - genetics / Vascular Endothelial Growth Factor Receptor-3 - metabolism