MUTATIONS IN THE PIG-A GENE CAUSING PARTIAL DEFICIENCY OF GPI-LINKED SURFACE-PROTEINS (PNH-II) IN PATIENTS WITH PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA

Paroxysmal nocturnal haemoglobinuria (PNH) is due to the absence or marked reduction of glycan phosphatidylinositol (GPI)-anchored proteins on the surface of blood cells that are completely deficient (PNH III) or partially deficient (PNH II) in these proteins, or they may have both. PNH III has recently been shown to be due, in all cases examined, to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor synthesis. We now show that two patients with PNH II cells also have somatic mutations of the same gene: these produce a partial rather than a total loss of PIG-A function.