胎儿α-地中海贫血无创基因检测的临床可行性研究  

Clinical Feasibility Study of Non-invasive Gene Detection of Fetalα-thalassemia

作　　者：刘洁 王晓贤 林雨虹 林伟 LIU Jie;WANG Xiao-xian;LIN Yu-hong(Fuzhou First Hospital Affiliated to Fujian Medical University,Fuzhou,Fujian,350009,China)

机构地区：[1]福建医科大学附属福州市第一医院,福建福州350009

出　　处：《黑龙江医学》2022年第22期2704-2706,2710,共4页Heilongjiang Medical Journal

基　　金：福州市科技局医疗卫生项目(2019-SZ-8)。

摘　　要：目的:探讨孕母血血浆游离胎儿DNA对胎儿α-地中海贫血(以下简称地贫)无创性产前诊断的临床可行性及价值。方法:选取2018年10月—2021年4月福建医科大学附属福州市第一医院就诊及转诊的22个α-地贫基因携带家系的孕妇作为研究对象,对孕妇行羊膜腔穿刺术抽取羊水,进行产前诊断,运用反向点杂交的方法进行地贫基因型诊断,并以此为金标准。运用区域捕获结合高通量测序技术,通过检测孕妇外周血血浆中游离胎儿DNA(circulation free fetal DNA,cffDNA)无创产前检测的方法获得胎儿地贫基因型,将其与金标准结果进行比对,比较二者的一致性,从而推论孕妇外周血血浆cff-DNA对诊断胎儿缺失型α-地中海贫血的准确性及可行性。结果:22个家系中胎儿基因型在无创产前检测和有创产前诊断结果完全一致。其中2个家系中,无创产前基因检测不仅可以检测缺失型突变,还可以检测点突变。无创产前基因检测可以排除与母体不同型的父源突变。结论:基于二代测序的无创产前基因检测技术在胎儿α-地中海贫血基因无创性检测中具有较好的可行性,有望在孕6周的时候获得胎儿地贫基因结果,实现安全、无创、准确、简便及早期诊断,避免一定的流产和宫内感染的风险,具有较好的前景。Objective:To investigate the clinical feasibility and value of non-invasive prenatal diagnosis of fetalα-thalassemia by plasma cell-free fetal DNA in maternal blood.Methods:22 pregnant women withα-thalassemia gene-carrying families who were seen and referred by the hospital from October 2018 to April 2021 were selected as the research subjects.The pregnant woman and her husband signed informed consent.Amniocentesis was performed on pregnant women to extract amniotic fluid for prenatal diagnosis,and reverse dot hybridization was used to diagnose thalassemia genotype,which was regarded as the gold standard.By region capture combined with high-throughput sequencing technology,the genotype of fetal thalassaemia was obtained by non-invasive prenatal detection of Circulation Free fetal DNA(cffDNA)in the peripheral blood plasma of pregnant women.It was compared with the gold standard results to compare the consistency of the two,so as to infer the accuracy and feasibility of the maternal peripheral blood plasma cff-DNA in the diagnosis of fetal deletionα-thalassemia.Results:The results of non-invasive prenatal testing and invasive prenatal diagnosis of fetal genotype in 22 families were completely consistent.In 2 of these families,non-invasive prenatal genetic testing can detect not only deletion mutations but also point mutations.Noninvasive prenatal genetic testing can rule out paternal mutations that are different from the maternal type.Conclusion:The non-invasive prenatal genetic detection technology based on next-generation sequencing has good feasibility in the non-invasive detection of fetalα-thalassemia gene.It is expected to obtain fetal thalassemia gene results at the 6th week of pregnancy,to achieve safe,non-invasive,accurate,simple and early diagnosis,to avoid certain risks of miscarriage and intrauterine infection,and has a good prospect.

关 键 词：巴氏胎儿水肿综合征 无创产前诊断 地中海贫血 东南亚缺失型 

分 类 号：R556[医药卫生—血液循环系统疾病]