2 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 geneti c disease affecting 3% of the total Chinese population in Taiwan. To i nvestigate the molecular basis of this deficiency, ive 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 Chines e. The first, G6PD Miaoli, involved a C-->G substitution at nucleotide (nt) 519, producing a Phe(173) to Leu change in the protein. The seco nd mutation (G6PD Keelung) involved a C-->T change at nt 1387, resulti ng in an Arg(163) to Cvs substitution. The F8C/G6PD (coagulation facto r VIIIc) haplotype that spans the Xq28 region from the gene for coagul ation factor VIIIc to the gene for G6PD was also investigated in Chine se using PCR and restriction enzyme digestion. Of the 16 possible hapl otypes, only four were found, which suggests that these four polymorph ic sites are in strong linkage disequilibrium. Analysis of the associa tion of G6PD mutations with F8C/G6PD haplotype revealed that nt 517, 5 92, 535, and 1387 mutations are linked to haplotype VI+VII, whereas th e nt 519 mutation is linked to haplotype III. The finding that some G6 PD mutations are associated with a particular F8C/G6PD haplotype may b e useful for future population studies.