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.
Haematologica
; 91(5): 589-95, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16670064
ABSTRACT
BACKGROUND AND OBJECTIVES:
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. DESIGN ANDMETHODS:
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. INTERPRETATION ANDCONCLUSIONS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Pré-Leucemia
/
Leucemia-Linfoma Linfoblástico de Células Precursoras B
/
Receptores de Fator Estimulador de Colônias de Granulócitos
/
Elastase de Leucócito
/
Proteínas de Neoplasias
/
Neutropenia
Tipo de estudo:
Etiology_studies
Limite:
Adult
/
Child
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Suécia