What question did this study set out to answer?

The aim is to understand the genetic basis of lymphatic anomalies and their effects on lymphatic vessel development.

March 3, 2014Open Access

Genetics of lymphatic anomalies

PBPascal BrouillardPrincess Anne Hospital LBLaurence M. BoonBoston Children's Hospital MVMiikka VikkulaUniversité Claude Bernard Lyon 1

Key Points

The aim is to understand the genetic basis of lymphatic anomalies and their effects on lymphatic vessel development.
Analysis of germline mutations in at least 20 genes related to lymphatic anomalies.
Investigating the impact of mutations on VEGFR-3 signaling and downstream pathways.
Utilizing murine models to assess the physiological implications of mutations.
Germline mutations account for over 25% of primary lymphedema cases, particularly inherited forms.
Mutations affect RAS/MAPK and PI3K/AKT signaling pathways.
Most murine knockouts for relevant genes are homozygous lethal, indicating distinct differences in lymphatic physiology.

Abstract

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.

问 AI

Bookmark

View Full Paper