Paroxysmal nocturnal hemoglobinuria: an acquired X-linked genetic disease with somatic-cell mosaicism

Curr Opin Genet Dev. 2006 Jun;16(3):317-22. doi: 10.1016/j.gde.2006.04.015. Epub 2006 May 2.


Paroxysmal nocturnal hemoglobinuria (PNH) is a severe hemolytic anemia caused by an intrinsic abnormality of the red blood cells that makes them exceedingly susceptible to the lytic action of activated complement (C). This abnormality results from a mutation in the PIG-A gene on Xp22. Given that the mutation is not inherited but is somatically acquired by a hematopoietic stem cell, it creates two populations of blood cells: normal cells and PNH cells. The clinical expression of PNH depends on the relative and absolute expansion of the PNH cell population, which probably depends, in turn, on a paradoxical growth advantage conferred to it by the existence in the patients of an autoimmune process that exerts negative selection against the 'normal' hematopoietic stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity / genetics
  • Autoimmunity / immunology
  • Cell Lineage
  • Genetic Diseases, X-Linked / genetics*
  • Hemoglobinuria, Paroxysmal / diagnosis
  • Hemoglobinuria, Paroxysmal / genetics*
  • Hemoglobinuria, Paroxysmal / immunology
  • Hemoglobinuria, Paroxysmal / pathology*
  • Humans
  • Membrane Proteins / genetics
  • Mosaicism*


  • Membrane Proteins
  • phosphatidylinositol glycan-class A protein