Inborn errors of the development of human natural killer cells

Curr Opin Allergy Clin Immunol. 2013 Dec;13(6):589-95. doi: 10.1097/ACI.0000000000000011.


Purpose of review: 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).

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Deaminase / deficiency*
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / immunology
  • Adenylate Kinase / genetics
  • Adenylate Kinase / immunology
  • Agammaglobulinemia / genetics*
  • Agammaglobulinemia / immunology*
  • Agammaglobulinemia / pathology
  • Agammaglobulinemia / physiopathology
  • GATA2 Transcription Factor / genetics
  • GATA2 Transcription Factor / immunology
  • Humans
  • Janus Kinase 2
  • Janus Kinase 3 / genetics
  • Janus Kinase 3 / immunology
  • Killer Cells, Natural
  • Minichromosome Maintenance Complex Component 4 / genetics
  • Minichromosome Maintenance Complex Component 4 / immunology
  • Mycobacterium Infections / genetics
  • Mycobacterium Infections / immunology
  • Mycobacterium Infections / pathology
  • Mycobacterium Infections / physiopathology
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / pathology
  • Severe Combined Immunodeficiency / physiopathology
  • Virus Diseases / genetics
  • Virus Diseases / immunology
  • Virus Diseases / pathology
  • Virus Diseases / physiopathology


  • GATA2 Transcription Factor
  • GATA2 protein, human
  • JAK2 protein, human
  • JAK3 protein, human
  • Janus Kinase 2
  • Janus Kinase 3
  • Adenylate Kinase
  • adenylate kinase 2
  • ADA protein, human
  • Adenosine Deaminase
  • MCM4 protein, human
  • Minichromosome Maintenance Complex Component 4

Supplementary concepts

  • Severe combined immunodeficiency due to adenosine deaminase deficiency