A novel G6PD deleterious variant identified in three families with severe glucose-6-phosphate dehydrogenase deficiency

Background Glucose-6-phosphate dehydrogenase deficiency (D-G6PD) is an X-linked recessive disorder resulted from deleterious variants in the housekeeping gene Glucose-6-phosphate 1-dehydrogenase (G6PD), causing impaired response to oxidizing agents. Screening for new variations of the gene helps with early diagnosis of D-G6PD resulting in a reduction of disease related complications and ultimately increased life expectancy of the patients. Methods One thousand five hundred sixty-five infants with pathological jaundice were screened forG6PDvariants by Sanger sequencing all of the 13 exons, and the junctions of exons and introns of theG6PDgene. Results We detectedG6PDvariants in 439 (28.1%) of the 1565 infants with pathological jaundice. In total, 9 types ofG6PDvariants were identified in our cohort; and a novelG6PDmissense variant c.1118 T > C, p.Phe373Ser in exon 9 of theG6PDgene was detected in three families. Infants with this novel variant showed decreased activity of G6PD, severe anemia, and pathological jaundice, consistent with Class IG6PDdeleterious variants. Analysis of the resulting protein's structure revealed this novel variant affects G6PD protein stability, which could be responsible for the pathogenesis of D-G6PD in these patients. Conclusions High rates ofG6PDvariants were detected in infants with pathological jaundice, and a novel Class IG6PDdeleterious variants was identified in our cohort. Our data reveal that variant analysis is helpful for the diagnosis of D-G6PD in patients, and also for the expansion of the spectrum of knownG6PDvariants used for carrier detection and prenatal diagnosis.