Characteristics of G6PD mutations in newborns with G6PD deficiency from 2021 to 2022 in Heze, China

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits distinct regional and ethnic heterogeneity. The molecular characteristics of G6PD deficiencies in Heze, Shandong Province, China, are unclear. In this study, we explored the incidence and genetic mutations characteristic of G6PD deficiencies in newborns in Heze to investigate the pathogenicity of new G6PD mutations. We measured G6PD activity in 114,285 neonates born in Heze and identified 80 patients with G6PD deficiencies. G6PD mutations were analyzed using Sanger sequencing. Functional studies were conducted by constructing eukaryotic expression vectors, transfecting them into HEK-293T and HELA cells, and measuring the mRNA and protein levels and G6PD enzymatic activity. The incidence of G6PD deficiency was 0.07% (80/114,285). We identified 17 mutation types with a 100% G6PD mutation detection rate, including four mutations not reported previously in the Chinese population: c.682G>A, c.479G>A, c.404A>T, and c.486-7C>G. The heterozygous missense mutations c.479G>A/p.S160N and c.404A>T/p.N135I increased mRNA levels, decreased protein expression, and reduced G6PD activity. Neonatal G6PD deficiency in Heze is rare, and the most commonly mutated loci were c.1388G>A, c.487G>A, and c.1376G>T. Four novel G6PD mutations were identified, of which c.479G>A/p.S160N, and c.404A>T/p.N135I are potentially pathogenic. These mutations may cause G6PD deficiency via different mechanisms, thereby requiring further experimental investigation.