无创DNA检测技术对胎儿染色体非整倍体疾病的筛查效果

Noninvasive DNA testing technology in the application of the fetal chromosomal aneuploidy disease

目的探讨无创DNA产前检测技术在胎儿染色体非整倍体疾病中的临床应用。方法将2011年12月—2 014年12月在空军总医院产前门诊,经知情同意自愿接受无创DNA产前检测的2 0 78例单胎自然妊娠孕妇作为研究对象。检测方法从孕妇外周血中提取胎儿游离DNA并进行PCR扩增后利用最新的高通量测序技术,推算出胎儿患染色体非整倍体疾病(如21-三体、18-三体、13-三体综合征等)的风险率。对检测高风险者行产前咨询,建议行羊水穿刺等确诊手段,随访其妊娠结局。结果无创DNA产前检测异常者23例。10例提示21-三体高风险,2例提示18-三体高风险,1例提示18-三体临界高风险,3例提示13-三体高风险,3例提示性染色体异常(2例提示45,X0;1例提示47,XXY),4例提示其他染色体异常(2例7号染色体偏多,1例16号染色体偏多,1例17号染色体偏多)。经羊水穿刺检查确诊为胎儿非整倍体疾病者11例。确诊病例分别为21-三体6例;18-三体2例;13-三体2例;47,XXY 1例。另外,2例DNA检测提示异常,羊水穿刺检查结果阴性,随访妊娠结局未见异常。应用无创DNA产前检测技术筛查胎儿染色体非整倍体异常的灵敏度为10 0%,特异度为99.81%,假阳性率为0.19%,假阴性率为0%。结论无创DNA产前检测技术能够对胎儿染色体非整倍体疾病进行准确筛查,值得推广。

Objective To evaluate the role of noninvasive prenatal detection of DNA technology in the clinical application of fetal chromosomal aneuploidy disease.Methods A total of 2 078 pregnant women of natural singletons pregnancy who approved of accepting noninvasive prenatal detection of DNA in antenatal clinics,Air Force General Hospital antenatal clinics were recruited for this study from December 2011 to December 2014.The method collected peripheral blood of pregnant women,extracted cell-free fetal DNA,and used PCR amplification,then applied a new generation of high-throughput sequencing technology to find out the risk rate of fetal suffering from fetal chromosomal aneuploidy diseases（such as Down＇ s syndrome,Trisomy 18 syndrome,Trisomy 13 syndrome）.Consultation was given to those whose detection results were at high risk,diagnostic means such as amniotic fluid puncture were suggested,and the pregnancy outcomes were followed up.Results We found a total of 23 cases of noninvasive prenatal detection of DNA abnormal：10 cases suggested high risk of Down＇ s syndrome,2 cases suggested high risk of Trisomy 18 syndrome,1 case suggested critical risk of Trisomy 18 syndrome,3 cases suggested high risk of Trisomy 13 syndrome,3 cases suggested sex chromosome abnormality（2 cases suggested 45,X0;1 case suggested 47,XXY）,4 cases prompted other chromosomal abnormalities（2 cases suggested chromosome 7 bullish,1 case of chromosome 16 bullish,1 case of chromosome 17 bullish）.Amniotic fluid puncture examination confirmed 11 cases of fetal chromosomal aneuploidy disease.11 cases of confirmed fetal chromosomal aneuploidy disease contained 6 cases of Down＇ s syndrome;2 cases of Trisomy 18 syndrome;2 cases of Trisomy 13 syndrome;1 case of 47,XXY.2 cases of noninvasive genetic tests prompted abnormal,but amniotic fluid puncture examination was normal,then by following up their pregnancy outcomes,no abnormalities were found.The sensitivity of noninvasive prenatal detection of DNA technology in the diagnosis of chromosomal aneuploidy abnormality was 100%,the specificity was 99.81%,the false positive rate was 0.19%,and the false negative rate was 0%.Conclusion Noninvasive prenatal detection of DNA technology is noninvasive and accurate in screening for fetal chromosomal aneuploidy disease,having clinical value.