ZFIN ID: ZDB-PUB-180206-7
Somatic NRAS mutation in patient with generalized lymphatic anomaly
Manevitz-Mendelson, E., Leichner, G.S., Barel, O., Davidi-Avrahami, I., Ziv-Strasser, L., Eyal, E., Pessach, I., Rimon, U., Barzilai, A., Hirshberg, A., Chechekes, K., Amariglio, N., Rechavi, G., Yaniv, K., Greenberger, S.
Date: 2018
Source: Angiogenesis   21(2): 287-298 (Journal)
Registered Authors: Yaniv, Karina, Ziv, Limor
Keywords: Lymphangiomatosis, Mutation, NRAS
MeSH Terms:
  • Animals
  • Endothelial Cells*
  • Extracellular Signal-Regulated MAP Kinases/genetics
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • GTP Phosphohydrolases*/genetics
  • GTP Phosphohydrolases*/metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lymphatic Vessels/abnormalities
  • Lymphatic Vessels/metabolism
  • Lymphatic Vessels/pathology
  • Membrane Proteins*/genetics
  • Membrane Proteins*/metabolism
  • Mice
  • Mice, SCID
  • Mutation*
  • TOR Serine-Threonine Kinases/genetics
  • TOR Serine-Threonine Kinases/metabolism
  • Zebrafish
PubMed: 29397482 Full text @ Angiogenesis
ABSTRACT
Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.
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