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1: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4480-4.Click here to read Links

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

Dong F, Hoefsloot LH, Schelen AM, Broeders CA, Meijer Y, Veerman AJ, Touw IP, Löwenberg B.

Dr. Daniel den Hoed Cancer Center, Department of Hematology, Rotterdam, The Netherlands.

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.

PMID: 7514305 [PubMed - indexed for MEDLINE]

PMCID: PMC43809