Two novel glucose 6-phosphate dehydrogenase deficiency mutations and association of such mutations with F8C/G6PD haplotype in Chinese.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disease affecting 3% of the total Chinese population in Taiwan. To investigate the molecular basis of this deficiency, we analyzed blood samples from G6PD-deficient newborns using a nonradioactive polymerase chain reaction coupled with single-stranded conformation polymorphism (PCR-SSCP) analysis. We identified two novel G6PD mutations in Chinese. The first, G6PD Miaoli, involved a C-->G substitution at nucleotide (nt) 519, producing a Phe173 to Leu change in the protein. The second mutation (G6PD Keelung) involved a C-->T change at nt 1387, resulting in an Arg463 to Cys substitution. The F8C/G6PD (coagulation factor VIIIc) haplotype that spans the Xq28 region from the gene for coagulation factor VIIIc to the gene for G6PD was also investigated in Chinese using PCR and restriction enzyme digestion. Of the 16 possible haplotypes, only four were found, which suggests that these four polymorphic sites are in strong linkage disequilibrium. Analysis of the association of G6PD mutations with F8C/G6PD haplotype revealed that nt 517, 592, 835, and 1387 mutations are linked to haplotype VI+VII, whereas the nt 519 mutation is linked to haplotype III. The finding that some G6PD mutations are associated with a particular F8C/G6PD haplotype may be useful for future population studies.