Point Mutations Result in Glucose - 6 - Phosphate Dehydrogenase ( G 6 PD ) Polymorphism in Taiwan

Glucose-6-PHOSPHATE dehydrogenase (GGPD; EC 1.1.1.49) deficiency is the most common human enzymopathy, affecting more than 200 million people worldwide. Although greater than 400 variants have been described based on clinical and biochemical criteria, little is known about the molecular basis of these GGPD deficiencies. Recently, the gene that encodes human G6PD has been cloned and sequenced, which enables us to examine directly the heterogeneity of G6PD at the DNA level. During the past 10 years, we examined the G6PD activity in 21,271 newborn Chinese infants (11,400 males and 9,871 females) and identified 314 (2.8%) males and 246 (2.5%) females having low GGPD activity. The G6PD gene from 10 randomly selected affected individuals and their relatives was polymerase chain reaction (PCR) amplified, subcloned, and sequenced. Our results indicate that at least four types of mutation are responsible for the G6PD polymorphism in Taiwan. The first type of mutation (487 G -+ A) was found in an affected Chinese with a G to A change at nucleotide 487, which results in a (163)Gly to Ser substitution. The second type of mutation (493 A -+ G) is a novel mutation that has not been reported in any other