MUTATIONS IN THE PIG-A GENE LEAD TO GPI DEFICIENCY IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the deficiency of glycosylphosphatidylinositol-(GPI-)anchored surface molecules on blood cells. The biochemical basis of this deficiency is the lack of the first GPI biosynthesis intermediate GlcNAc-PI in the deficient cells corresponding to that in Thy-1- mouse lymphoma mutants of the class A. Recently, the responsible gene (PIG-A gene) has been cloned. Here, PIG-A transcripts in T-, NK- and EBV-transformed B cell lines of different PNH patients have been analyzed. In contrast to the uniform biochemical defect, these molecular analyses reveal heterogenous mutations of the PIG-A gene in different PNH patients.