Abstract
BackgroundGlucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; however, no study has investigated the genetic basis of G6PDD in the Qatari population yet.MethodsIn this study, we analyzed whole-genome sequencing data generated by the Qatar Genome Programme for 6045 Qatar Biobank participants, to identify G6PDD variants in the Qatari population. In addition, we assessed the impact of the novel variants identified on protein function both in silico and by measuring G6PD enzymatic activity in the subjects carrying them.ResultsWe identified 375 variants in/near G6PD gene, of which 20 were high-impact and 16 were moderate-impact variants. Of these, 14 were known G6PDD-causing variants. The most frequent G6PD-causing variants found in the Qatari population were p.Ser188Phe (G6PD Mediterranean), p.Asn126Asp (G6PD A +), p.Val68Met (G6PD Asahi), p.Ala335Thr (G6PD Chatham), and p.Ile48Thr (G6PD Aures) with allele frequencies of 0.0563, 0.0194, 0.00785, 0.0050, and 0.00380, respectively. Furthermore, we have identified seven novel G6PD variants, all of which were confirmed as G6PD-causing variants and classified as class III variants based on the World Health Organization’s classification scheme.ConclusionsThis is the first study investigating the molecular basis of G6PDD in Qatar, and it provides novel insights about G6PDD pathogenesis and highlights the importance of studying such understudied population.
Highlights
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world
Malik et al Hum Genomics (2021) 15:61 activity < 1%), class II is considered severe and associates with acute hemolytic anemia (G6PD activity < 10%), class III is considered as moderate deficiency and it is associated with occasional acute hemolytic anemia (G6PD activity of 10–60%), while classes IV and V are asymptomatic (G6PD activity of 60–150% and > 150%, respectively) [5]
G6PDD affects around 400 million people globally making it the most common human enzymopathy [6]; it is common in the Middle East with prevalence rates reaching up to 39.8% and 30% in Saudi Arabia and Syria, respectively [7, 8]
Summary
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is the most common red cell enzymopathy in the world. In Qatar, the incidence of G6PDD is estimated at around 5%; no study has investigated the genetic basis of G6PDD in the Qatari population yet. Glucose-6-phosphate dehydrogenase (G6PD) is an omnipresent cytosolic enzyme that has an important housekeeping role in all cells. In red blood cells (RBCs), nicotinamide adenine dinucleotide phosphate (NADPH) is produced mainly by the action of G6PD in the first. No studies addressed the molecular basis of G6PDD in Qatar. We investigated G6PDD-causing variants in the Qatari population using whole-genome sequencing (WGS) data from Qatar Genome Programme (QGP) for 6,045 Qatar Biobank (QBB) participants [11]
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