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Title: Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia

Abstract

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 the authors 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. This mutant receptor chain may act in a dominant negative manner to block granulocytic maturation. 40 refs., figs., 2 tabs.

Authors:
;  [1]; ; ; ;  [2]; ;  [3]
  1. Dr. Daniel den Hoed Cancer Center, Rotterdam (Netherlands)
  2. Erasmus Univ., Rotterdam (Netherlands)
  3. Free Univ., Amsterdam (Netherlands)
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
50646
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 91; Journal Issue: 10; Other Information: PBD: 10 May 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; NEUTROPHILS; MATURATION; CELL PROLIFERATION; RECEPTORS; GENE MUTATIONS; GROWTH FACTORS

Citation Formats

Dong, F, Loewenberg, B, Erasmus Univ., Rotterdam, Hoefsloot, L H, Schelen, A M, Broeders, C A.M., Touw, I P, Meijer, Y, and Veerman, A J.P. Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. United States: N. p., 1994. Web. doi:10.1073/pnas.91.10.4480.
Dong, F, Loewenberg, B, Erasmus Univ., Rotterdam, Hoefsloot, L H, Schelen, A M, Broeders, C A.M., Touw, I P, Meijer, Y, & Veerman, A J.P. Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. United States. https://doi.org/10.1073/pnas.91.10.4480
Dong, F, Loewenberg, B, Erasmus Univ., Rotterdam, Hoefsloot, L H, Schelen, A M, Broeders, C A.M., Touw, I P, Meijer, Y, and Veerman, A J.P. 1994. "Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia". United States. https://doi.org/10.1073/pnas.91.10.4480.
@article{osti_50646,
title = {Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia},
author = {Dong, F and Loewenberg, B and Erasmus Univ., Rotterdam and Hoefsloot, L H and Schelen, A M and Broeders, C A.M. and Touw, I P and Meijer, Y and Veerman, A J.P.},
abstractNote = {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 the authors 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. This mutant receptor chain may act in a dominant negative manner to block granulocytic maturation. 40 refs., figs., 2 tabs.},
doi = {10.1073/pnas.91.10.4480},
url = {https://www.osti.gov/biblio/50646}, journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 10,
volume = 91,
place = {United States},
year = {Tue May 10 00:00:00 EDT 1994},
month = {Tue May 10 00:00:00 EDT 1994}
}