Somatic NRAS mutation in patient with generalized lymphatic anomaly

Eugenia Manevitz-Mendelson, Gil S. Leichner, Ortal Barel, Inbal Davidi-Avrahami, Limor Ziv-Strasser, Eran Eyal, Itai Pessach, Uri Rimon, Aviv Barzilai, Abraham Hirshberg, Keren Chechekes, Ninette Amariglio, Gideon Rechavi, Karina Yaniv, Shoshana Greenberger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish
Pages (from-to)287-298
Number of pages12
Issue number2
StatePublished - 1 May 2018


FundersFunder number
Israel Science Foundation1716/11
March of Dimes
Marie Curie Re-integrationFP7-PEOPLE-2010-IRG
March of Dimes Foundation5-FY12-55
FP7 People: Marie-Curie ActionsPEOPLE-2010-IR
Israel Science Foundation


    • Lymphangiomatosis
    • Mutation
    • NRAS


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