Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia.
Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony-stimulating factor receptor (G-CSF-R). We have described a case with constitutive extracellular G-CSF-R mutation hyporesponsive to ligand. Here we report two independent acquired G-CSF-R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co-expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G-CSF-R mutant, while constitutively-active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G-CSF.
School of Medicine, Deakin University, Geelong, Vic., Australia. award@deakin.edu.au
Alister C
AC
Ward
Judith
J
Gits
Fidel
F
Majeed
Andrew A
AA
Aprikyan
Rowena S
RS
Lewis
Lynda A
LA
O'Sullivan
Melvin
M
Freedman
Sarah
S
Shigdar
Ivo P
IP
Touw
David C
DC
Dale
Yigal
Y
Dror
D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009503:Neutropenia / Q000151:congenital* / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050799:STAT5 Transcription Factor; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; C117309:pancreatic elastase II