目的 对广西柳州新生儿进行葡萄糖-6-磷酸脱氢酶活性筛查及G6PD基因多态性检测,为遗传咨询及精准诊断提供理论依据。方法 收集2016年6月-2017年12月在柳州市妇幼保健院新生儿疾病筛查中心进行新生儿疾病筛查的足跟干滤纸血片81 112例进行葡萄糖-6-磷酸脱氢酶活性定量分析,选取2 595例阳性结果中的329例,及酶活性筛查正常女性新生儿50例,采用多色探针荧光PCR熔解曲线法进行中国人最常见的12种G6PD基因多态性(95A>G、383T>C、392G>T、487G>A、517T>C、592C>T、 871G>A、1004C>A、1024C>T、1360C>T、1376G>T、1388G>A)检测。结果 329例酶活性筛查阳性样本中男性236例,女性93例,检出野生型样本28例(男性9例,女性19例),基因突变301例(91.5%),其中包括男性半合子突变227例,女性纯合突变7例,女性复合杂合突变20例,女性杂合突变47例。基因突变类型分布:95A>G突变71例,392G>T突变1例,517T>C突变1例,592C>T突变1例,871G>A 突变12例,1004C>A突变3例,1024C>T突变31例,1360C>T 突变1例,1376G>T突变69例,1388G>A 突变111例,未发现383T>C及487G>A突变。50例酶活性筛查正常女性新生儿检出杂合突变携带者4例。结论 G6PD基因1388G>A、95A>G、1376G>T突变为本地区常见突变类型,基因诊断可有效检出女性杂合子携带者,建议表型和基因型结合的筛查方法,提高女性杂合子的检出率。
Abstract
Objective To explore incidence gene types of glucose-6-phosphate dehydrogenase deficiency,and provide the support for genetic counseling and clinical medication.Methods We found 81 112 neonates who were newborn screened by glucose 6 phosphate dehydrogenase quantitative testing during the period from June 2016 to December 2017 in Liu zhou Maternal and Child Health Hospital,329 blood samples were collected from 2 595 suspected patients,and 50 blood samples of female neonates who were newborn screened by glucose 6 phosphate dehydrogenase quantitative testing were normal. G6PD gene were analyzed by multiplex probe melting curve to detect the 12 types common G6PD gene mutations.Results There were 301 cases detected gene mutation in 329 cases (236 male, 93 female) of samples. Multiplex probe melting curve has detected 28 wild type samples(9 male, 19 female),227 male hemizygous mutation samples,7 female homozygous mutation samples,20 female compound heterozygous mutation samples and 47 female heterozygous mutation samples. Find 10 different mutation types:71 cases of 95A>G(23.6%),1 cases of 392G>T(0.33%),1 cases of 517T>C(0.33%),1 cases of 592C>T(0.33%),12 cases of 871G>A(3.99%),3 cases of 1004C>A(0.99%),31 cases of 1024C>T(10.3%),1 cases of 1360C>T(0.33%),69 cases of 1376G>T(22.9%),111 cases of 1388G>A(36.9%),383T>C and 487G>A mutations were not detected. 4 female heterozygous mutation samples were detected form 50 female neonates.Conclusion 1388G>A、95A>G and 1376G>T are the most common types of G6PD gene mutation in Guangxi Liuzhou, multiplex probe melting curve analysis for G6PD gene mutation is sensitive for diagnosis female heterozygous mutation.
关键词
葡萄糖-6-磷酸脱氢酶缺乏症 /
G6PD基因 /
女性 /
新生儿
Key words
glucose-6-phosphate dehydrogenase deficiency /
G6PD gene /
female /
neonate
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Yan T,Cai R,Mo O,et al.Incidence and complete molecular characterization of glucose-6-phosphate dehydrogenase deficiency in the Guangxi Zhuang autonomous region of southern China:description of four novel mutations[J].Haematologica,2006,91(10):1321-1328.
[2] 林芬,杨辉,杨立业.我国葡萄糖-6-磷酸脱氢酶缺乏症的分布特征和基因突变[J].分子诊断与治疗杂志,2016,8(2):73-77.
[3] 张力佳,熊符.G6PD 缺乏症的分子病理学新机制[J].国际遗传学杂志,2011,34 (5):271-276.
[4] 杜传书,王菁,陈路明,等.中国人中所见的六种葡萄糖-6-磷酸脱氢酶基因的点突变[J] .中华血液学杂志,1993,14(8):395-398.
[5] 郑敏,罗建明.广西地区 G6PD 缺乏症患儿的基因突变型与临床表现[J] .中国妇幼保健,2007,22(10):1329-1330 .
[6] 郑咏梅,张琴.广东壮族瑶族和汉族人群 G6PD 缺乏症的基因频率调查[J] .新医学,2003,34(3):144-145.
[7] 周海燕.粤北地区葡萄糖- 6-磷酸脱氢酶缺乏症基因突变频率研究[J].国际检验医学杂志,2011,32(9):1011-1013.
[8] 吴新秀,杨学煌,曾宪琪,等.荧光 PCR 熔解曲线法检测广东韶关地区 G6PD 缺乏症基因突变[J].湖南师范大学学报:医学版,2017,14(3):174-177.
[9] 刘秀莲,王洁,黄慈丹,等.海口地区新生儿G6PD基因突变分析[J].分子诊断与治疗杂志,2017,9(3):165-167.
[10] 任锡麟,修瑾,何燕,等.少数民族葡萄糖-6-磷酸脱氢酶基
因突变检测[J].中国公共卫生,2004,20(6):672-673.
[11] 齐晓岚,单可人,谢渊,等 . 贵州省从江县侗族人群葡萄糖-6-磷酸脱氢酶基因突变型的检测[J].中国地方病学杂志,2006,25(3):283-285.
[12] Jiang J,Li B,Cao W,et al. Screening and prevention of neonatal glucose-6-Phosphate dehydrogenase deficiency in Guangzhou,China[J].Genet Mol Res,2014,13 (2):4272-4279.
[13] 严提珍,钟青燕,唐宁,等.多色探针荧光 PCR熔解曲线法在G6PD基因突变检测中的临床应用评价[J].中华医学遗传学杂志,2014,31(2):156-162.
[14] 蒋明.葡萄糖-6-磷酸脱氢酶缺乏症的分子机制及诊断方法研究进展[J].国际检验医学杂志,2012,33(23):2894-2896.
基金
柳州市应用技术研究与开发课题(2017BH20313); 广西壮族自治区卫生和计划生育委员会科研课题(Z20170532);柳州市科技攻关项目(2014G020404)
PDF(22277 KB)
