Somatic mosaicism in primary immune deficiencies

Curr Opin Allergy Clin Immunol. 2008 Dec;8(6):510-4. doi: 10.1097/ACI.0b013e328314b651.


Purpose of review: Spontaneous genetic reversions and second-site mutations resulting in revertant somatic mosaicism are poorly understood phenomena with a seemingly frequent occurrence in primary immunodeficiency diseases. Here we summarize the several cases that have been reported thus far with particular focus on the most recent observations.

Recent findings: Revertant cells have been associated with attenuated clinical phenotypes in some, although not all, immunodeficient patients who presented with somatic mosaicism. Interestingly, the latest studies suggest that revertant cells may also be responsible for immune dysregulation. In addition, extensive molecular analysis of revertant cells has revealed that an unexpectedly large variety of genetic changes can be responsible for their emergence.

Summary: The occurrence of revertant somatic mosaicism in patients affected with primary immunodeficiency diseases is likely much more common than originally anticipated. The study of this fascinating phenomenon continues to provide clues as to the possible underlying mechanisms and to inform, albeit indirectly, the process of development of cell and gene therapy for these diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Chromosomes, Human, Pair 12
  • Codon, Nonsense
  • DNA Repair / immunology
  • Genetic Predisposition to Disease
  • Humans
  • Immunologic Deficiency Syndromes / blood
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / pathology
  • Infant, Newborn
  • Mosaicism*
  • Risk Factors
  • Wiskott-Aldrich Syndrome / blood
  • Wiskott-Aldrich Syndrome / genetics*
  • Wiskott-Aldrich Syndrome / pathology


  • Codon, Nonsense