SOMATIC MUTATIONS OF PIG-A IN THAI PATIENTS WITH PAROXYSMAL-NOCTURNALHEMOGLOBINURIA

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by clonal blood cells that are deficient in th e surface expression of glycosylphosphatidylinositol (GPI)-anchored pr oteins. In the affected cells, the X-chromosomal gene PIG-A, which par ticipates in biosynthesis of the GPI anchor, is somatically mutated. A nalyses of Japanese, British, and American patients with PNH have show n somatic mutations of PIG-A in all of them, indicating that PIG-A is responsible for PNH in most, if not all, patients in those countries. Twenty-nine of the reported somatic mutations are small, mostly involv ing 1 or 2 bases, except for one with a 4-kb deletion. Here we describ e an analysis of PIG-A in neutrophils from 14 patients from Thailand w here PNH is thought to be more common. We found small somatic PIG-A mu tations in all patients. These consisted of six single base deletions, one each of 2-, 3-, 5- and 10-base deletions, two single base inserti ons and two base substitutions. Thus, the small somatic mutation in th e PIG-A gene is also responsible for PNH in Thailand. However, base su bstitutions were rarer (2 of 14) than in Japan (8 of 16), and deletion s of multiple bases were more common, suggesting various causes of mut ation. (C) 1995 by The American Society of Hematology.