New genetic discoveries and primary immune deficiencies

Clin Rev Allergy Immunol. 2014 Apr;46(2):145-53. doi: 10.1007/s12016-013-8380-0.


The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • Genetic Association Studies
  • Genetic Therapy*
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / therapy*
  • Mutation / genetics
  • Phenotype
  • Receptors, CXCR4 / genetics
  • Signal Transduction / genetics


  • CD3 Complex
  • CXCR4 protein, human
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors
  • Receptors, CXCR4