Deletional mutation of the external domain of the human granulocyte colony-stimulating factor receptor in a patient with severe chronic neutropenia refractory to granulocyte colony-stimulating factor.

Abstract	Severe chronic neutropenia (SCN) is characterized by a profound neutropenia, which mostly presents during the neonatal period. The precise genetic basis of SCN remains elusive. Acquired somatic mutations involving the carboxy-terminus of the G-CSF receptor (G-CSFR) have been found, often in association with myelodysplastic syndrome. The authors describe a girl with SCN who did not respond to pharmacologic doses of filgrastim. Genetic analysis of bone marrow and germline cells revealed a 182-bp deletion in the extracellular domain of the G-CSFR. Co-precipitation studies showed an association between the wild-type and mutant G-CSFR, confirmed by their co-localization by confocal microscopy. Coexpression of the mutant receptor inhibited the wild-type response in Ba/F3 cells. These findings establish a novel constitutional defect in the G-CSFR that supports a partial dominant negative mechanism for receptor dysfunction in SCN.
Authors	Srish Sinha, Quan Sheng Zhu, Guillermo Romero, Seth J Corey
Journal	Journal of pediatric hematology/oncology (J Pediatr Hematol Oncol) Vol. 25 Issue 10 Pg. 791-6 (Oct 2003) ISSN: 1077-4114 [Print] United States
PMID	14528102 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Receptors, Granulocyte Colony-Stimulating Factor Recombinant Proteins Granulocyte Colony-Stimulating Factor Filgrastim
Topics	Amino Acid Sequence Animals Base Sequence Cell Division (drug effects) Cell Line, Tumor Child, Preschool Female Filgrastim Granulocyte Colony-Stimulating Factor (pharmacology, therapeutic use) Humans Infant, Newborn Mice Molecular Sequence Data Neutropenia (drug therapy, genetics, metabolism, pathology) Polymerase Chain Reaction Precipitin Tests Protein Binding Protein Structure, Tertiary (genetics) Receptors, Granulocyte Colony-Stimulating Factor (chemistry, genetics) Recombinant Proteins Sequence Deletion (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!