【摘要】 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准确性。方法选择2011年10月至2013年9月于佛山市妇幼保健院行无创性非整倍性产前基因检测的2433例名孕妇,孕周12-24w,均为单胎,年龄21-41岁。对无创性非整倍性筛查高风险的孕妇行羊膜腔穿刺或脐静脉血穿刺,行常规染色体核型分析。对筛查结果低风险者行电话随访其胎儿出生后情况,统计分析无创性产前非整倍性检测的准确性。结果 2433例孕妇中,母体血浆胎儿游离DNA高通量测序技术检测出42例胎儿染色体非整倍性高风险。其中33例通过羊膜腔穿刺或脐静脉血穿刺对比分析,27例21三体高风险者行有创性产前诊断,26例为47,XN,+21,1例为46,XN。2例18三体高风险者行进一步确诊,其中1例为47,XN,+18,1例为46,XN。2例13三体高风险孕妇结果均与穿刺结果为46,XN。1例X0高风险孕妇与穿刺结果为45X[25]/46,XX[25]。1例XXY高风险孕妇结果为47,XXY。孕妇血浆中游离胎儿DNA检测结果阴性者2391例,经电话随访有效者2145例,截止至2014年4月30日,已出生的新生儿均未发现唐氏综合征患儿。无创性非整倍体检测对常见染色体非整倍体的检出率100%,灵敏度100%,特异度99.8,假阳性率0.33%,假阴性率为0,阳性预测值87.9%。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。更多还原

【Abstract】 Objective:To determine the feasibility and accuracy of detecting chromosomal aneuploidy by high-flux sequencing analysis of free fetal DNA from maternal plasma.Methods:Chromosomalaneuploidies in fetalfree DNAs from 2433 cses of pregnant women were detected noninvasively by high-flux sequencing in our center from October 2011 to September 2013.The positive results were validated by cordocentesis or amniocentesis based karyotypeing.The negative results were followed up until the babies were born.Results:42 cases with high risk of chromosomal aneuploidy were detected by high-flux sequencing analysis,among which 33 were validated by karyotyping.29 cases were confirmed to be chromosomal aneuploidy(26cases of 47,XN,+21,1case of 47,XN,+18,1case of 47,XXY,1 case of mosaic(45,X[25]/46,XX[25])).The sensibility is 100% and the false positive rate is 0.33%;The specificity is 99.8% and the positive predictive value is 87.9%.Conclusion:High-flux sequencing analysis of free fetal DNA derived from maternal plasma is efficient for detecting fetal chromosomal aneuploidies,highly sensitive and specific.Therefore it has a broad application in prenatal diagnosis.更多还原