Mutation analysis of glucose-6-phosphate dehydrogenase (G6PD) variants in Costa Rica

Summary Glucose-6-phosphate dehydrogenase (G6PD) deficiency has previously been reported among both the black and white populations of Costa Rica. All 28 G6PD A — samples were found to be of the common G6PD A-^376G/202Atype. A previously described mutation associated with nonspherocytic hemolytic anemia, G6PD Puerto Limón, was found to be due to a GA transition at nucleotide (nt) 1192, causing a glulys substitution. Mutations in this region of the G6PD molecule seem invariably to be associated with chronic hemolytic anemia. G6PD Santamaria had been described previously in two unrelated white subjects. We found that both did, indeed, have the same mutations. In this variant the AG substitution at nt 376 that is characteristic of G6PD A was present, but an AT mutation at nt 542, apparently superimposed on the ancient G6PD A mutation, resulted in an aspval substitution. Thus, the gain of a negative charge at amino acid 126 was counterbalanced by the loss of a charge at amino acid 181, giving rise to a variant with the G6PD A mutation but with normal electrophoretic mobility.