title: Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden.
abstract: OBJECTIVE
  Severe congenital neutropenia (SCN) or Kostmann syndrome was originally reported to be an autosomal recessive disease of neutrophil production causing recurrent, life-threatening infections. Mutations in the neutrophil elastase gene (ELA-2) have previously been identified in patients with sporadic or autosomal dominant SCN.
  
  
  METHODS
  We studied 14 individuals (four patients with SCN and ten close relatives) belonging to the original Kostmann family in northern Sweden for mutations in the ELA-2 and the granulocyte colony-stimulating factor (G-CSF) receptor genes.
  
  
  RESULTS
  One patient belonging to the original Kostmann family harbored a novel heterozygous ELA-2 mutation (g.2310T-->A;Leu92His) that was not inherited from her parents. The mutation was identified in DNA isolated from both whole blood and skin fibroblasts, suggesting a sporadic de novo mutation. As a young adult this patient sequentially acquired two mutations in the gene for the G-CSF receptor (G-CSFR) and therefore recently received a hematopoietic stem cell transplant, due to the risk of evolution to leukemia. Moreover, another patient developed acute leukemia and was treated with transplantation. No pathogenic ELA-2 or G-CSFR gene mutations were found in this patient or the other two patients, nor in any healthy relative.
  
  
  CONCLUSIONS
  Our data are the first to document leukemia evolution and G-CSFR gene mutations in the original Kostmann kindred. In addition, our findings indicate that ELA-2 mutations are not the primary cause of SCN in the Swedish Kostmann family.
authors: Department of Woman and Child Health, Karolinska University Hospital Solna, Stockholm, Sweden.
authors: Göran
authors: G
authors: Carlsson
authors: Andrew A G
authors: AA
authors: Aprikyan
authors: Kim Göransdotter
authors: KG
authors: Ericson
authors: Steve
authors: S
authors: Stein
authors: Vahagn
authors: V
authors: Makaryan
authors: David C
authors: DC
authors: Dale
authors: Magnus
authors: M
authors: Nordenskjöld
authors: Bengt
authors: B
authors: Fadeel
authors: Jan
authors: J
authors: Palmblad
authors: Jan-Inge
authors: JI
authors: Hentera