PIG-A GENE-MUTATIONS IN 4 TAIWANESE PATIENTS WITH PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA FOLLOWING APLASTIC-ANEMIA

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic d isorder caused by deficient biosynthesis of the glycosyl phosphatidyli nositol (GPI) anchor in haemopoietic stem cells. PIG-A, an X-linked ge ne that participates in the first step of GPI-anchor synthesis, is res ponsible for PNH. Various abnormalities of the PIG-A gene have been de monstrated in all patients with PNH so far examined. In this study we characterized the somatic mutations in PIG-A gene in four Taiwanese pa tients with PNH. We identified five novel mutations in the PIG-A gene, three single nucleotide substitution mutations (-342, C --> G, codon 335, GGT --> AGT and codon 405, GCT --> GTT) and two frameshift mutati ons (codon 22, GGA --> G-A and codon 356, TGT --> TGTT) in the PIG-A g ene. The -342 mutation was judged to be a polymorphism. Furthermore, t hree patients had previous clinicopathologic evidence which suggested aplastic anaemia (AA), before the development of PNH. One of these was found to have thrombocytopenia during follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup of AA having a patho genetic link with PNH.