[Paroxysmal nocturnal hemoglobinuria and its association with aplastic anemia].
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of haematopoiesis. Clinically it is characterized by intravascular haemolysis, venous thrombosis and often by bone marrow hypoplasia. Haemolysis and thrombosis develop as a consequence of deficiency of several proteins on the cell membrane of the affected clone of blood elements. This is caused by somatic mutations in the PIG-A gene, which encodes an enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchor. Spectrum of mutations in the PIG-A gene is different to that observed in other genes. The mutations are mainly small deletions and insertions causing frameshift; large deletions are rare. Recently, however, a 88 base pairs direct tandem repeat insertion has been reported in a patient with PNH developed on the background of aplastic anaemia (AA). The peculiar pattern of the PIG-A gene mutations and the finding that more than one mutated clone is commonly present in patients with PNH might suggest that some form of hypermutability, caused by decreased DNA stability, deficient repair or increased generation of mutagens, might underline PNH. As most mutations cause cell death, it would explain the hypoplastic nature of the disorder and its association with AA. Other models of pathogenesis of PNH are also discussed.
Pavlů
J
J
Ustav patologické fyziologie, Praha.
Necas
E
E
D000741:Anemia, Aplastic / Q000150:complications* / Q000503:physiopathology; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D009154:Mutation