Genetics of lymphatic anomalies

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. Ge...

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Bibliographic Details
Published in:The Journal of clinical investigation 2014-03, Vol.124 (3), p.898-904
Main Authors: Brouillard, Pascal, Boon, Laurence, Vikkula, Miikka
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI71614