http://hdl.handle.net/1765/8531

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


Article
Related Files
asset icon
(7514305.pdf, 1.5MB)

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.



Keywords


Automatically Extracted Terms
  • patient
  • g-csf-r
  • g-csf
  • receptor
  • mutation
  • marrow cells
  • marrow
  • l-gm cells
  • blood
  • signal
  • point mutation
  • neutropenia
  • g-csf-r cdna
  • colony
  • g-csf signal transduction
  • factor
  • wild-type
  • sscp analysis
  • progenitor cells
  • analysis


Bookmark with: