Abstract

Aim: Paroxysmal nocturnal haemoglobinuria (PNH) is caused by deficient biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in haemopoietic stem cells. Mutation of the phosphatidylinositol glycan class A (PIG-A) gene, an X linked gene that participates in the first step of GPI anchor biosynthesis, is responsible for PNH. The characteristics of somatic mutation of the PIG-A gene in Korean patients with PNH were studied.

Methods: Twenty four patients with PNH were selected. Ham tests and sucrose haemolysis tests were carried out on all patients. The expression of CD59 in erythrocytes and granulocytes was investigated in 14 and five patients, respectively, to confirm the diagnosis. Dideoxy fingerprinting (ddF) was used to screen mutations, and direct sequencing of DNA was performed to characterise the mutations.

Results: Gene mutation was detected in 12 of the 24 patients. The other 12 patients were negative in ddF screening. Ten new mutations and two known mutations were detected. The mutations consisted of five deletions, six substitutions, and one insertion. These mutations resulted in six premature terminations, three abnormal splicings, one missense mutation in exon 2, and two nonsense mutations. Two patients with venous thrombosis showed mutations in exon 3 only. Substitution mutations were seen in six patients and frameshift mutations in the other six.

Conclusions: There were 10 new mutations among the 12 mutations in the Korean patients with PNH and the characteristics of the mutations varied, with no significant hot spots in sites or types.