海南省新生儿葡萄糖-6-磷酸脱氢酶缺乏症发生情况及基因突变分析研究

背景　葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症会因遇到某些诱因而引起急性的溶血性贫血，严重者可危及生命。海南省是G6PD缺乏症的高发地区，并且该病具有地域和种族特异性，通过筛查和最终基因确诊可做到积极有效的预防。但是目前还未见海南省人群G6PD缺乏症基因层面的报道。目的　调查2017年度海南省新生儿G6PD缺乏症发生率，并分析其基因突变特点。方法　选取全海南省内各助产单位2017-01-01至2017-12-31出生的活产新生儿130 512例。采集符合纳入标准的新生儿的足跟血制成滤纸干血片用于G6PD基因初筛。对于初筛可疑样本，采用G6PD/6-磷酸葡萄糖脱氢酶（6GPD）比值法进行生化检查确诊。生化检查确诊为G6PD缺乏症的患儿，找出其干血片进行基因分型。结果　2017年度海南省全省新生儿G6PD缺乏症初筛样本中初筛阳性率为4.00%（5 221/130 512），G6PD/6GPD确诊2 993例，经基因检测该2 993例新生儿均有G6PD基因突变。海南省新生儿G6PD/6GPD确诊G6PD缺乏症发生率和G6PD基因突变率均为2.29%（2 993/130 512）。G6PD/6GPD确诊G6PD缺乏症发生率汉族为1.80%（1 972/109 590），黎族为5.28%（934/17 698），其他民族为2.70%（87/3 224）。黎族G6PD缺乏症发生率高于汉族（χ2=826.206，P<0.001）。本次共检出10种基因突变类型：1 636例（54.66%）c.1376G>T，659例（22.02%）c.1388G>A，254例（8.49%）c.95A>G，204例（6.82%）c.1024C>T，93例（3.11%）c.871G>A，64例（2.14%）c.519C>T，25例（0.84%）c.392G>T，22例（0.74%）c.1360C>T，19例（0.63%）517T>C，11例（0.37%）c.592C>T，并检出8例（0.27%）c.1376G>T复合c.1388G>A突变，3例（0.10%）c.1376G>T复合c.871G>A突变，3例（0.10%）c.1376G>T复合c.517T>C突变。并发现5例（0.17%）未知突变，其中1例487G>A、1例1004C>A和1例c.86C>T，在海南省人群未见报道。结论　海南省新生儿G6PD缺乏症发生率较高，且显著高于汉族。同时，G6PD缺乏症基因突变类型以c.1376G>T、c.1388G>A、c.95A>G 和c.1024C>T为主；且发现5例未知突变，其中c.86C>T、c.487G>A和c.1004C>A突变各有1例。

Occurrence and Gene Mutation of Glucose-6-phosphate Dehydrogenase Deficiency in Neonates in Hainan Province

Background　Glucose-6-phosphate dehydrogenase （G6PD） deficiency can cause acute hemolytic anemia，which can endanger life in severe cases.Hainan Province is a region with high incidence of G6PD deficiency，and the disease has regional and racial specificity.Through screening and final genetic diagnosis，severe consequences of this disease can be actively and effectively prevented.At present，there is no report of the genetic study of G6PD deficiency in Hainan population.Objective　To find out the incidence and gene mutation characteristics of neonatal G6PD deficiency in Hainan province in 2017.Methods　A total of 130 512 live births from January 1，2017 to December 31，2017 were selected from all deliver units in Hainan Province.Samples of dry blood spot on filter paper were collected from heel blood of newborns who met the inclusion criteria for G6PD gene screening.The suspicious samples were screened for biochemical diagnosis by G6PD/6GPD ratio method.Children with G6PD deficiency confirmed by biochemical examination were divided into different genotypes by dry blood samples.Results　In 2017，the positive rate of G6PD primary screening was 4.00% （5 221/130 512） in Hainan province.A total of 2 993 cases of G6PD/6GPD deficiency were confirmed.All 2 993 cases had G6PD gene mutation detected by gene test.The diagnostic rate of G6PD/6GPD and the mutation rate of G6PD gene were both 2.29% （2 993/130 512） in Hainan province.The incidence of G6PD/6GPD deficiency was 1.80%（1 972/109 590） in Han nationality，5.28% （934/17 698） in Li nationality and 2.70% （87/3 224） in other nationalities.The incidence of G6PD deficiency in Li nationality was higher than that in Han nationality （χ2=826.206，P<0.001）．Ten types of gene mutations were：c.1376G>T of 1 636 cases （54.66%），c.1388G>A of 659 cases （22.02%），c.95A>G of 254 cases （8.49%），c.1024 C>T of 204 cases （6.82%），c.871G>A of 93 cases （3.11%），c.519 C>T of 64 cases （2.14%），c.392G>T of 25 cases （0.84%），c.1360C>T of 22 cases （0.74%），C>T of 19 cases （0.63%），c.592C>T of 11 cases （0.37%），and c.1376G>T combined c.1388G>A mutation of 8 cases （0.27%），c.1376G>T combined c.871G>A mutation of 3 cases（0.10%），and c.1376G>T combined c.517T>C mutation of 3 cases（0.10%）.Five（0.17%） unknown mutations were found，including 1 case of 487G>A，1 case of 1004C>A and 1 case of c.86C>T，which were not reported in Hainan province.Conclusion　The prevalence of G6PD deficiency in neonates in Hainan is high，and the incidence of G6PD deficiency in Li nationality was significantly higher than that in Han nationality.The mutations of G6PD gene are mainly c.1376G>T，c.1388G>A，c.95A>G and c.1024 C>T.Five unknown mutations were found，including c.86C>T，c.487G>A and c.1004C>A.