Zhang Xin, Duan Yanan, Zhang Xiao, Li Miaomiao, Li Ling, Zhang Renwei, Liu Shiguo
Department of Medical Genetics, Affiliated Hospital of Qingdao University, Qingdao, China.
Prenatal Diagnosis Center of Qingdao University Affiliated Hospital, Qingdao, China.
Front Immunol. 2025 Apr 17;16:1472474. doi: 10.3389/fimmu.2025.1472474. eCollection 2025.
Glucose-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.
We 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.
The 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.
The 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.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症在分布上具有明显的区域和种族异质性，而关于中国山东省菏泽地区G6PD缺乏症分子特征的信息有限。我们旨在探讨菏泽地区新生儿G6PD酶缺乏症的发病率和基因突变特征，以研究新的G6PD突变的致病性。
我们检测了菏泽地区出生的114,285名新生儿的G6PD活性，并确定了80例G6PD缺乏症患者。使用桑格测序法分析这些患者G6PD的基因突变。通过构建真核表达载体，将其转染到HEK-293T和HELA细胞中，并测量mRNA和蛋白质水平以及G6PD酶活性来进行功能研究。
研究人群中G6PD缺乏症的发病率为0.07%（80/114,285）。我们鉴定出17种突变类型，G6PD突变检测率为100%，其中四种具有显著性：c.479G>A、c.404A>T和c.486-7C>G为全球新突变，而c.682G>A此前在中国从未有过报道。功能研究表明，杂合错义突变c.479G>A/p.S160N和c.404A>T/p.N135I增加了mRNA水平，降低了蛋白质表达，并降低了G6PD活性。
菏泽地区新生儿G6PD缺乏症的发病率较低，最常见的突变位点为c.1388G>A、c.487G>A和c.1376G>T。在这些突变中，c.479G>A/p.S160N和c.404A>T/p.N135I具有潜在致病性。这些突变可能通过不同机制导致G6PD缺乏，因此需要进一步的实验研究。
