Y. Azenishi et al., CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia, BR J HAEM, 104(3), 1999, pp. 523-529
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.