1994
Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia
Publication
Publication
Proceedings of the National Academy of Sciences of the United States of America
Severe congenital neutropenia (Kostmann syndrome) is characterized by profound absolute neutropenia and a maturation arrest of marrow progenitor cells at the promyelocyte-myelocyte stage. Marrow cells from such patients frequently display a reduced responsiveness to granulocyte-colony-stimulating factor (G-CSF). G-CSF binds to and activates a specific receptor which transduces signals critical for the proliferation and maturation of granulocytic progenitor cells. Here we report the identification of a somatic point mutation in one allele of the G-CSF receptor gene in a patient with severe congenital neutropenia. The mutation results in a cytoplasmic truncation of the receptor. When expressed in murine myeloid cells, the mutant receptor transduced a strong growth signal but, in contrast to the wild-type G-CSF receptor, was defective in maturation induction. The mutant receptor chain may act in a dominant negative manner to block granulocytic maturation.
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hdl.handle.net/1765/8531 | |
Proceedings of the National Academy of Sciences of the United States of America | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
Dong, F., Hoefsloot, L., Schelen, A., Broeders, C. A., Meijer, Y., Veerman, A. J., … Löwenberg, B. (1994). Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. Proceedings of the National Academy of Sciences of the United States of America. Retrieved from http://hdl.handle.net/1765/8531 |