摘要：
Objective To determine the feasibility and accuracy of detecting the chromosomal aneuploidy of free fetal DNA in maternal plasma by high-throughput sequencing.Methods High-throughput sequencing was applied to analyze the sequence copy numbers of fetal chromosome.Fetal karyotyping was also carried out for the amniocentesis samples.Consistency between the two methods was analyzed statistically.Results Eight cases were detected to be high risk of chromosomal aneuploidy by high-throughput sequencing,among which 6 cases were confirmed by karyotyping (3 cases of 47,XN,+ 21,1 case of 47,XN,+18,1 case of 47,XN,+ 13,1 case of 47,XXY,1 case of 47,XXX),1 case was confirmed to be mosaic (46,XN[2]/47,XN,+ 13[33]/47,XN,+ 13,add(15) (P12) [15]).The amniotic fluid cells from the 100 cases were cultured successfully (success rate was 100％).There was consistency between two methods (κ =0.928).The sensibility is 100％ and the false positive rate is 1.1％ ; The specificity is 98.9％ and the positive predictive value is 87.5％.Conclusion High-throughput sequencing is an efficient ways to detectfetal chromosomal aneuploidy.Therefore it has a broad application in prenatal diagnosis.%目的 探讨应用高通量测序技术对孕妇血浆胎儿游离DNA进行无创性胎儿染色体非整倍性检测的可行性和准确性.方法 采用高通量基因测序技术检测母体血浆胎儿游离DNA,分析胎儿染色体的非整倍性信息.同时行羊水常规染色体核型分析.统计分析两种方法检测结果的一致性.结果 100名孕妇中,母体血浆游离DNA平行测序技术检测出8例胎儿染色体非整倍性高风险.采集的100份羊水标本均培养成功,成功率为100％.共检测出7例胎儿染色体核型异常,其中染色体非整倍体异常6例(3例47,XN,+21;1例47,XN,+18;1例47,XN,+13;1例47,XXY;1例47,XXX);嵌合体1例(46,XN[2]/47,XN,+13[33]/47,XN,+13,add(15) (p12) [15]).无创基因检测与羊水染色体核型分析两种方法的κ=0.928(P ＜0.05),检测结果具有一致性.无创基因检测技术的假阳性率1.01％,灵敏度100％,特异度98.9％,阳性预测值87.5％.结论 应用高通量测序技术在染色体非整倍性无创性检测具有很高的灵敏性,假阳性率很低,在胎儿染色体非整倍性疾病的产前检测中具有广泛的应用前景.
