title: Inborn errors of the development of human natural killer cells.
abstract: OBJECTIVE
  Inborn errors of human natural killer (NK) cells may affect the development of these cells, their function, or both. There are two broad categories of genetic defects of NK cell development, depending on whether the deficiency is apparently specific to NK cells or clearly affects multiple hematopoietic lineages. We review here recent progress in the genetic dissection of these NK deficiencies (NKDs).
  
  
  RESULTS
  Patients with severe combined immunodeficiencies bearing mutations of adenosine deaminase, adenylate kinase 2, interleukin-2 receptor gamma chain, and Janus kinase 3 genes present NKDs and are prone to a broad range of infections. Patients with GATA binding protein 2 deficiency are susceptible to both mycobacterial and viral infections, and display NKDs and a lack of monocytes. Rare patients with mini chromosomal maintenance 4 deficiency display an apparently selective NKD associated with viral infections, but they also display various nonhematopoietic phenotypes, including adrenal insufficiency and growth retardation.
  
  
  CONCLUSIONS
  These studies have initiated a genetic dissection of the development of human NK cells. Further studies are warranted, including the search for genetic causes of NKD in particular. This research may lead to the discovery of molecules specifically controlling the development of NK cells and to improvements in our understanding of the hitherto elusive function of these cells in humans.
authors.affiliation: aLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Hospital for Sick Children bParis Descartes University, Imagine Institute, Paris, France cSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA dCenter for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden eCentre d'Immunologie de Marseille-Luminy, INSERM U1104 fCNRS UMR7280 gAix Marseille Université, UM2 hService d'Immunologie, Assistance Publique - Hôpitaux de Marseille, Hôpital de la Conception, Marseille iPediatric Hematology-Immunology Unit, Necker Hospital, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
authors.forename: Laure
authors.initials: L
authors.lastname: Gineau
authors.forename: Julien
authors.initials: J
authors.lastname: Cottineau
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000263:Adenylate Kinase / Q000235:genetics / Q000276:immunology; D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000276:immunology; D006801:Humans; D053614:Janus Kinase 2; D053616:Janus Kinase 3 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural; D064148:Minichromosome Maintenance Complex Component 4 / Q000235:genetics / Q000276:immunology; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D000263:Adenylate Kinase; C110938:adenylate kinase 2; C548482:ADA protein, human; D000243:Adenosine Deaminase; C099243:MCM4 protein, human; D064148:Minichromosome Maintenance Complex Component 4