The PIG-A gene somatic mutation responsible for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria is the first example of a non neoplastic human disease caused by the somatic mutation of an X-linked gene. The PIG-A gene maps to Xp22.1 and is required for the transfer of N-acetyl glucosamine to phosphoinositol, an early step in the production of the GPI anchor. A deficiency of GPI-linked proteins on the cell surface is responsible for the PNH cell defect, which can be detected by flow cytometry not only on red cells, but also on myeloid cells and in some patients even on lymphoid cells. Its location on the X-chromosome explains how a single recessive mutation can cause the appearance of the abnormal clone. A number of patients may have more than one PNH clone, suggesting that the expansion of GPI-deficient clones occurs under the pressure of a selection mechanism.