BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by deficient biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in hemopoietic stem cells. Mutation of phosphatidyl inositol glycan class A (PIG-A) gene, an X-linked gene that participates in the first step of GPI anchor biosynthesis, is responsible for PNH. Characteristics of somatic mutation of PIG-A gene in the Korean patients with PNH and their relationships to clinical characteristics were analyzed.
METHODS: Twenty five patients with PNH and a donor of bone marrow transplantation were selected. Ham tests, sucrose hemolysis tests and CD59 expressions of erythrocytes and granulocytes were performed to confirm diagnosis. Dideoxy fingerprinting (ddF) was used to screen mutations, and direct sequencing of DNA was performed to characterize the mutations.
RESULTS: The mutations of PIG-A gene were found in twelve cases and ten of them were novel mutations. There were five deletions, six substitutions and a insertion. There were six premature terminations, three abnormal splicings, a missense and two nonsense mutations. There were six point mutations and six frameshift mutations. Five cases of hypoplastic PNH showed mutations in exons, but three in seven cases of hemolytic PNH showed mutations in introns. Two cases with symptoms of venous thrombosis showed mutations in exon 3.
CONCLUSION: There were ten novel mutations among twelve mutations in the Korean patients with PNH and characteristics of the mutations were variable without any remarkable hot spot in sites and types. The characteristics of mutation were not correlated with the results of clinical courses of the patients with PNH.

Keywords: Paroxysmal nocturnal hemoglobinuria (PNH), Mutation, Phosphatidyl inositol glycan class A (PIG-A) gene, Glycosylphosphatidylinositol (GPI) anchor, Dideoxy fingerprinting (ddF),