CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia

Patients with aplastic anaemia (AA) frequently develop paroxysmal nocturnal haemoglobinuria (PNH) as a late complication. We investigated the frequenc y of the development of PNH features including a glycosyl phosphatidylinosi tol (GPI) anchoring defect in 73 Japanese patients with AA. A deficient exp ression of CD59 was found on erythrocytes and/or granulocytes in 21/73 (28. 8%) of the patients, A Ham/sugar water test was positive in 13/21 patients. We also examined mutations of the PIG-A gene in 11 patients with CD59 defi ciency. A heteroduplex analysis detected PIG-A gene abnormality in 10/11 pa tients tested. Nucleotide sequencing was performed in six patients and iden tified eight mutations including three mutations in one patient. The mutati ons of the PIG-A gene were all different and included two single-base inser tions, one single-base deletion, two two-base deletions, and one each of ei ght-base insertion and nine- and ten-base deletions. All mutations but one caused frameshifts. Our findings indicate that a high proportion of Japanes e patients with severe AA have a GPI-anchoring defect and that the PIG-A ge ne is mutated in the AX patients who had a GPI deficiency. We found no sign ificant difference in the pattern of the PIG-A gene mutation between the AA patients with a GPI deficiency and those with ne novo PNH.