hematology and oncology
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Etiology of PNH
Paroxysmal nocturnal hemoglobinuria is a clonal disorder caused by an acquired mutation in thePIGAgene in hematopoietic stem cells.PIGA, located on the X chromosome, encodes a protein that is integral for formation of the glycosylphosphatidylinositol (GPI) anchor for membrane proteins. Mutations inPIGAresult in loss of all GPI-anchored proteins, including CD59, an important complement-regulating protein, on the surface of blood cells. As a consequence, cells are susceptible to complement activation, leading to ongoing intravascular hemolysis of red blood cells (RBCs). 