葡萄糖-6-磷酸脱氢酶缺乏症女性杂合子基因突变检测的临床意义  

Clinical Significance of Gene Mutation Detection for Female Heterozygotes with Glucose-6-Phosphate Dehydrogenase Deficiency

作　　者：何英 陈雄豪 林广城 王琼[1] 凌利芬 陆学东[4] HE Ying;CHEN Xiong-Hao;LIN Guang-Cheng;WANG Qiong;LING Li-Fen;LU Xue-Dong(Department of Laboratorial Medicine,The Eighth Affiliated Hospital,SUN Yat-Sen University,Shenzhen 518033,Guangdong Province,China;Women and Children′s Healthcare Hospital of Futian District,Shenzhen 518026,Guangdong Province,China;The Seventh People′s Hospital of Longgang District,Shenzhen 518114,Guangdong Province,China;Center Laboratory,The Eighth Affiliated Hospital,SUN Yat-Sen University,Shenzhen 518033,Guangdong Province,China)

机构地区：[1]中山大学附属第八医院检验医学部,广东深圳518033 [2]深圳市福田区妇幼保健院,广东深圳518026 [3]深圳市龙岗区第七人民医院,广东深圳518114 [4]中山大学附属第八医院中心实验室,广东深圳518033

出　　处：《中国实验血液学杂志》2020年第5期1757-1761,共5页Journal of Experimental Hematology

基　　金：深圳市科技计划项目(JCYJ20160428175336440);深圳市福田区卫生公益科研项目(FTWS20160011)。

摘　　要：目的:探讨基因突变检测在检测葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症女性杂合子中的临床价值。方法:采用G6PD活性生化表型检测方法和核酸扩增导流杂交基因检测法对无血缘关系的女性血液标本分别进行G6PD活性检测和常见14种突变基因检测,对未检测到基因突变的G6PD阳性样本进行测序检测分析,对2种检测结果进行分析比较。结果:无血缘关系的女性体检者共493例接受检测,其中酶活性正常473例,酶活性降低20例,G6PD酶活性降低检出率为4.06%。全部受检女性中,130例女性检出G6PD基因突变,包括c.1311 C>T突变在内检出率为26.37%,致病基因突变检出率为8.11%,2种方法对女性G6PD缺乏症检出率有明显差异(P<0.01),G6PD酶活性检测可造成49.94%女性杂合子漏检。本研究共检出8种基因突变13种突变变异型,大多为单核苷酸替代错义突变,除单纯c.1311 C>T突变之外,最常见突变为c.1376G>T、c.1388G>A、c.95 A>G 3种突变。20例G6PD活性降低女性人群中,19例检测到致病基因突变,473例G6PD活性正常女性人群中,21例检测到致病基因突变,杂合子基因突变占90.88%。结论:G6PD酶活性检测不足以满足女性杂合子检测需要,采用覆盖本地区常见基因突变类型的基因检测方法可有效鉴定酶活性正常G6PD缺乏症女性杂合子人群。Objective:To explore the clinical significance of G6 PD gene mutation detection in female heterozygote with G6 PD deficiency.Methods:G6 PD activity and fourteen common G6 PD gene mutations in female blood samples were detected by biochemical phenotype detection and PCR-reverse dot blotting,respectively.Unidentified genotype of G6 PD positive samples was further ascertained by direct DNA sequencing.The results from two methods were compared and analyzed.Results:A total of 493 unrelated females were enrolled,and the G6 PD activity and G6 PD mutations was detected.Among them,473 females were found to be normal in G6 PD activity and 20 females with G6 PD deficiency,and the detection rate by G6 PD activity method was 4.06%.In all enrolled females,G6 PD gene mutations,including the mutation of c.1311 C>T,were identified in 130 females,and the detection rate was 26.3%.Detection rate of the mutations that can lead to G6 PD deficiency was 8.11%.The detection rates between the two methods were significantly different(P<0.01).The misdiagnosis rate of the G6 PD activity detection reached 49.94%for the female heterozygotes.Eight G6 PD mutations and 13 mutation patterns were identified in the research,and most of mutation patterns were single nucleotide missense mutation.In addition to c.1311 C>T mutation,the most common mutations were c.1376 G>T,c.1388 G>A and c.95 A>G.G6 PD mutations were identified in 19 of 20 females with G6 PD deficiency,and were also detected in 21 of 473 females with normal G6 PD activity,of which the rate of heterozygous mutation was 90.88%.Conclusion:The phenotype detection based on G6 PD enzyme activity alone is not sufficient for the diagnosis of female heterozygotes.The detection of G6 PD mutations that covers the common mutations in specified region can effectively identify the female heterozygotes with normal G6 PD activity.

关 键 词：葡萄糖-6-磷酸脱氢酶缺乏 女性杂合子 基因突变 

分 类 号：R596[医药卫生—内科学] R555[医药卫生—临床医学]