胎儿游离DNA在染色体非整倍体疾病无创产前筛查中的应用

Application of cell-free fetal DNA in noninvasive prenatal screening of chromosome aneuploidy

目的讨论母体外周血液中胎儿游离DNA在染色体非整倍疾病无创产前筛查中的意义。方法选取2015年6月1日至12月31日在我中心接受无创产前诊断的孕妇共1452例。根据血清学筛查,超声诊断结果,以及分娩年龄,将孕妇分为5组,其中唐筛高风险组277例,唐筛临界风险组278例,高龄妊娠组401例,超声异常组121例,自愿孕期筛查组375例。对所有孕妇抽取外周血,并利用高通量测序的方法进行胎儿游离DNA检测。无创DNA检测结果为阳性的孕妇,建议进行羊水染色体核型分析以确定胎儿染色体是否存在异常;无创DNA检测结果为阴性的孕妇进行电话随访。结果 5组孕妇共计1452例均完成了胎儿游离DNA检测,共检测出染色体异常胎儿23例,检出率为1.58%。其中21-三体阳性10例,18-三体阳性6例,13-三体阳性1例,性染色体异常6例。共有13例无创DNA检出结果异常的孕妇进行了羊水染色体核型分析,其中10例无创21-三体阳性的孕妇中,9例染色体核型分析结果为47,XN,+21,1例为46,XN;1例无创18-三体阳性的孕妇染色体核型分析结果为47,XN,+18;2例性染色体提示异常的,染色体核型分析结果均为正常。电话随访未发现染色体异常患儿。利用母血中胎儿游离DNA筛查染色体非整倍体胎儿的灵敏度为100%(10/10),特异度为99.79%(1429/1432)。结论利用母血中胎儿游离DNA对胎儿染色体非整倍体进行无创产前筛查具有较高的灵敏度及特异性,具有广泛意义和推广价值。但是仍存在一定的假阳性,且对性染色体异常的检测准确性仍然较低,应进一步结合其他产前诊断方法做出准确的判断。

Objective：To explore the value of cell-free fetal DNA in maternal plasma in the application of fetal prenatal screening of aneuploidy disease. Methods：We selected 1452 pregnant women from 1st,July,2015 to 31 st,December 2015 who came to the prenatal diagnosis center. All the pregnant women were separated into five groups according to results of ultrasound examination,erological screening and delivery ages,which are group with high risk including 277 women,group with critical risk including 278 women,group more than 35 years old including 401 women,group with abnormal ultrasound results including 121 women,and group of pregnancies who are willing to have prenatal screening including 376 pregnancies. Taking maternal peripheral blood and testing the cell free fetal DNA using high-throughput sequencing technology. For the pregnancies with positive results,amniocenteses were taken to analysis the fetal karyotype;for the pregnancies with negative results,the follow-up visits were carried out by phone. Results：All of 1452 pregnant women accomplished the cell-free fetal DNA examination. 23 fetuses were tested as positive results,the detective rate was 1.58%. Among which 1 case was trisomy 13,6 cases were trisomy 18,10 case were trisomy 21,as well as 6 cases were tested as sex chromosome abnormality. Among these pregnancies with positive results,13 of them taken the amniocentesis. Results of kyrotyping analysis showed that：9 out of 10 cases of trisomy21 were 47,XN,＋21,1 was 46,XN;1 case of trisomy 18 had the kayrotype of 47,XN,＋18;2 cases with sex chromosome abnormality showed the normal kayrotype result. Among the negative results,the follow-up visits did not find abnormal newborns. The cell free fetal DNA applied to prenatal aneuploidy screending has a sensitivity of 100%,and specificity of 99.79%. Conclusion：prenatal screening of fetal aneuploidy using cell free fetal DNA has a wide spread use and high value of popularization. However,there still exists false positive result,and the accuracy for detecting sex chromosome abnormality is also relatively low. In that case,other prenatal diagnosis should be combine to get accurate diagnosis.