Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China

IntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency has a distinct regional and ethnic heterogeneity in distribution, and information on the molecular characteristics of G6PD deficiencies in the Heze area, Shandong Province, China, is limited. We aimed to explore the incidence and geneti...

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Main Authors: Xin Zhang, Yanan Duan, Xiao Zhang, Miaomiao Li, Ling Li, Renwei Zhang, Shiguo Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472474/full
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author Xin Zhang
Xin Zhang
Xin Zhang
Yanan Duan
Yanan Duan
Yanan Duan
Xiao Zhang
Xiao Zhang
Miaomiao Li
Miaomiao Li
Ling Li
Renwei Zhang
Renwei Zhang
Shiguo Liu
Shiguo Liu
author_facet Xin Zhang
Xin Zhang
Xin Zhang
Yanan Duan
Yanan Duan
Yanan Duan
Xiao Zhang
Xiao Zhang
Miaomiao Li
Miaomiao Li
Ling Li
Renwei Zhang
Renwei Zhang
Shiguo Liu
Shiguo Liu
author_sort Xin Zhang
collection DOAJ
description IntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency has a distinct regional and ethnic heterogeneity in distribution, and information on the molecular characteristics of G6PD deficiencies in the Heze area, Shandong Province, China, is limited. We aimed to explore the incidence and genetic mutations characteristic of G6PD enzyme deficiencies in newborns in the Heze area to investigate the pathogenicity of new G6PD mutations.MethodsWe measured G6PD activity in 114,285 neonates born in the Heze area and identified 80 patients with G6PD deficiencies. The genetic mutations in G6PD in these patients 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.ResultsThe incidence of G6PD deficiency in the study population was 0.07% (80/114,285). We identified 17 mutation types with a 100% G6PD mutation detection rate, with four of them being significant: c.479G>A, c.404A>T, and c.486-7C>G being globally novel mutations, while c.682G>A has never been reported in China before. Functional studies revealed that 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.DiscussionThe incidence of neonatal G6PD deficiency in the Heze area is low, and the most commonly mutated loci were c.1388G>A, c.487G>A, and c.1376G>T. Among these mutations, 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.
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publisher Frontiers Media S.A.
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spelling doaj-art-666591d18b0b42c4a9bd4d038447e60a2025-08-20T02:13:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.14724741472474Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of ChinaXin Zhang0Xin Zhang1Xin Zhang2Yanan Duan3Yanan Duan4Yanan Duan5Xiao Zhang6Xiao Zhang7Miaomiao Li8Miaomiao Li9Ling Li10Renwei Zhang11Renwei Zhang12Shiguo Liu13Shiguo Liu14Department of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaDepartment of Biochemical Laboratory, Heze Medical College, Heze, ChinaDepartment of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaDepartment of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaDepartment of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaLaboratory Department, Heze Municipal Hospital, Heze, ChinaDepartment of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaDepartment of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, ChinaPrenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, ChinaIntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency has a distinct regional and ethnic heterogeneity in distribution, and information on the molecular characteristics of G6PD deficiencies in the Heze area, Shandong Province, China, is limited. We aimed to explore the incidence and genetic mutations characteristic of G6PD enzyme deficiencies in newborns in the Heze area to investigate the pathogenicity of new G6PD mutations.MethodsWe measured G6PD activity in 114,285 neonates born in the Heze area and identified 80 patients with G6PD deficiencies. The genetic mutations in G6PD in these patients 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.ResultsThe incidence of G6PD deficiency in the study population was 0.07% (80/114,285). We identified 17 mutation types with a 100% G6PD mutation detection rate, with four of them being significant: c.479G>A, c.404A>T, and c.486-7C>G being globally novel mutations, while c.682G>A has never been reported in China before. Functional studies revealed that 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.DiscussionThe incidence of neonatal G6PD deficiency in the Heze area is low, and the most commonly mutated loci were c.1388G>A, c.487G>A, and c.1376G>T. Among these mutations, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472474/fullG6PDpathogenic variantglucose-6-phosphate dehydrogenase deficiencyHeze areanew mutation site
spellingShingle Xin Zhang
Xin Zhang
Xin Zhang
Yanan Duan
Yanan Duan
Yanan Duan
Xiao Zhang
Xiao Zhang
Miaomiao Li
Miaomiao Li
Ling Li
Renwei Zhang
Renwei Zhang
Shiguo Liu
Shiguo Liu
Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
Frontiers in Immunology
G6PD
pathogenic variant
glucose-6-phosphate dehydrogenase deficiency
Heze area
new mutation site
title Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
title_full Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
title_fullStr Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
title_full_unstemmed Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
title_short Characteristics of glucose-6-phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the Heze area of China
title_sort characteristics of glucose 6 phosphate dehydrogenase mutations in newborns with deficiency from 2021 to 2022 in the heze area of china
topic G6PD
pathogenic variant
glucose-6-phosphate dehydrogenase deficiency
Heze area
new mutation site
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472474/full
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