title: Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil?
abstract: OBJECTIVE
  Severe congenital neutropenia is a primary immunodeficiency in which lack of neutrophils causes inadequate innate immune host response to bacterial infections. Severe congenital neutropenia occurs with sporadic, autosomal dominant, autosomal recessive and X-linked recessive inheritance, as well as in a variety of multisystem syndromes. A principal stimulus for this review is the identification of novel genetic defects and pathophysiological insights into the role of neutrophil apoptosis.
  
  
  RESULTS
  The recent findings include identification of mutations in HAX1 in autosomal recessive severe congenital neutropenia (Kostmann disease), a large epidemiological study estimating the risk of progression from severe congenital neutropenia to leukemia, a better understanding of how heterozygous mutations in neutrophil elastase (ELA2) cause severe congenital neutropenia, molecular characterization of a novel syndromic form of severe congenital neutropenia called p14 deficiency and new animal models for several syndromic forms of severe congenital neutropenia.
  
  
  CONCLUSIONS
  We consider the numerous genes mutated in severe congenital neutropenia, the many attempts to make animal models of severe congenital neutropenia, and the results from both human and mouse studies investigating the molecular mechanisms of neutrophil apoptosis. Investigations of how severe congenital neutropenia genes and apoptosis pathways are connected should lead to a better understanding of the pathogenesis of neutropenia and apoptosis pathways relevant to many cell types.
authors.affiliation: Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010196:Pancreatic Elastase / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human; D011506:Proteins; D010196:Pancreatic Elastase