Paroxysmal nocturnal hemoglobinuria: an acquired X-linked genetic disease with somatic-cell mosaicism.
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.
Luzzatto
Lucio
L
University of Genova Scientific Director Istituto Toscano Tumori, Via Taddeo Alderotti 26N, 50139 Firenze, Italy. lucio.luzzatto@unige.it
D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009030:Mosaicism
D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein