Abstract: Objective　To analyze the characteristics of gene mutations of glucose-6-phosphate dehydrogenase（G6PD） deficiency in the neonates of Zhejiang Province，and discuss the genetic diversity. Methods　A total of 2242 G6PD values and blood stains on dry filter were collected from the children borned in Zhejiang Province with positive screening of G6PD deficiency between March 2015 and September 2017 in Neonatal Metabolic Screening Center of Zhejiang Province. Genomic DNA of the stains were extracted. Thirty-five gene mutation sites were detected by MassARRAY technology. The relationship between mutation gene sites and G6PD activity were analyzed by SPSS 22.0，taking P＜0.05 as the difference with statistical significance. Results　The mutation detection rate was 96.47%（2163/2242），including 96.51%（1995/2067） in males and 96%（168/175） in females. A total of 21 mutation sites 44 mutant genotypes were found，including 19 kinds of male hemizygote，14 kinds of female heterozygous，3 female homozygous type and 8 female complex heterozygous type. About 95.93% of G6PD mutations were located in exons 12，9，2，5，among which c.1376G＞T，c.1388G＞A，c.1024C＞T，c.95A＞G，c.871G＞A and c.392G＞T accounted for 92.96%. There were statistically significant differences in G6PD activity of c.1376G＞T，c.1388G＞A，c.1024C＞T，c.95A＞G （P＜0.0001）. Conclusion　There are mutation hotspots in G6PD deficiency in Zhejiang Province. The mutation frequency of c.1024C＞T has obvious regional characteristics. Using MassARRAY technology to detect specific mutation sites can be a choice as a second-level screening method for G6PD deficiency.

Key words: glucose-6-phosphate dehydrogenase, G6PD activity, G6PD mutation sites, MassARRAY technology, second-level screening method

摘要： 目的　分析浙江地区新生儿葡萄糖-6-磷酸脱氢酶（glucose-6-phosphate dehydrogenase，G6PD）缺乏症的基因突变特点，探讨其遗传多样性。方法　以2015年3月至2017年9月在浙江地区出生、经浙江省新生儿遗传代谢筛查中心G6PD缺乏症筛查发现的2242例患儿为对象，收集其新生儿筛查的G6PD活性值与剩余干滤纸血斑，并提取其血斑的基因组DNA。采用MassARRAY技术检测35个G6PD突变位点。采用SPSS 22.0软件统计分析基因型与G6PD活性的关系，P＜0.05为差异有统计学意义。结果　2163例检出突变，总检出率为96.47%，其中男性为96.51%（1995/2067），女性为96%（168/175）。共检出21种突变位点，44种变异基因型，其中男性半合子19型，女性杂合子14型，女性纯合子3型，女性复合杂合8型。95.93%的G6PD突变位于12、9、2、5外显子，其中c.1376G＞T、c.1388G＞A、c.1024C＞T、c.95A＞G、c.871G＞A、c.392G＞T占92.96%。c.1376G＞T、c.1388G＞A、c.1024C＞T、c.95A＞G四种基因型的G6PD活性差异有统计学意义（P＜0.0001）。结论　浙江地区G6PD缺乏症存在基因突变热点，c.1024 C＞T的突变频率具有明显地域特征，MassARRAY技术检测特定G6PD突变位点可推荐为G6PD缺乏症的二级筛查方法之一。

关键词: 葡萄糖-6-磷酸脱氢酶缺乏症, G6PD活性, G6PD突变位点, MassARRAY技术, 二级筛查