| Summary: | <p>Abstract</p> <p>Background</p> <p>Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency is caused by one or more mutations in the <it>G6PD</it> gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established.</p> <p>Methods</p> <p>In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females) who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction.</p> <p>Results</p> <p>All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr) was the most common variant in the cohort (30% in males patients) followed by the Mediterranean variant (p.Ser188Phe) detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both) were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females) were identified. Five of these were previously unreported (Jeddah A, B, C, D and E) and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency.</p> <p>Conclusions</p> <p>Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.</p>
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