目的 探讨新一代测序技术的新型无创DNA产前检测在诊断胎儿染色体非整倍体疾病中的应用价值。方法 2012年8月1日至2013年4月30日在安徽省妇幼保健院接受孕妇外周血中游离胎儿DNA检测者1365例，均为单胎，孕周(19.1±5.8)周，按照孕妇年龄及血清学筛查结果分为唐氏综合征筛查(唐筛)高危组、高龄组和其他原因组3组由北京贝瑞和康生物技术有限公司和湖南湘雅医院产前诊断中心合作开展的“大规模基于新一代测序技术的新型无创DNA产前检测”，对孕妇外周血中游离胎儿DNA进行序列分析，对检测结果阳性者进行羊水穿刺及胎儿染色体核型分析；对检测结果阴性者行电话随访其胎儿出生后情况。结果 ①3组孕妇共计1365例均成功完成游离胎儿DNA检测，检测结果为阳性者共33例，包括21三体19例、18三体8例、45，X 6例。其中唐筛高危组检出21三体8例、18三体7例、45，X 4例；高龄组检出21三体9例、18三体1例、45，X 2例；超声侧脑室增宽检出21三体1例、鼻骨缺失检出21三体一例。②游离胎儿DNA检测结果异常的33例孕妇中，28例进行了羊膜腔穿刺及染色体核型分析。19例21三体检测阳性者18例进行了羊膜腔穿刺，17例染色体核型均为47,XN,+21，另1例核型为46,XN(70)/47,XN,+21(10)，最后经胎儿脐血染色体检测为46，XN，随访新生儿正常。胎儿鼻骨缺失发现时已24周，无创检出21三体，行脐带血检测结果为异位型21三体，核型46，XX，der(21；21)(q10；q10)，+21。结果检出率100%，准确率94.4%。8例18三体检测阳性者中有7例进行了羊膜腔穿刺，7例核型为47,XN,+18；两者结果完全一致，另l例拒绝羊水穿刺，引产中发现胎儿全身水肿。6例45，X 检测阳性者中有3例进行了羊膜腔穿刺，2例核型为45,X，1例为46,XX（出现了假阳性），另3例拒绝羊水穿刺，其敏感性和准确性无法统计。③3组孕妇血浆中游离胎儿DNA检测结果阴性者1312例，经电话随访，截止至2012年4月30日，已出生的新生儿经检查均未发现唐氏综合征患儿。结论 孕妇外周血中游离胎儿DNA检测对21三体和18三体的检测准确率达96%，对45，X 的检出率也达到了很高水准，准确率有待临床配合进一步证实。但是在其他染色体异常的检测中还需要进一步研究。此外该方法不能筛查出染色体结构异常。
Objective To explore the value of a Massively Parallel Genomic Sequencing Technology, a new type of non-invasive prenatal diagnosis was applied on fetal chromosomal aneuploidy disease. Method 1365 singleton pregnant women with gestational age among from 13～25 weeks tested for free fetal DNA in peripheral blood, of whom 1051 had high risk in Down’s syndrome biochemical screening , 294 more than 35 years old, 10 were shown fetal abnormalities by ultrasound and 10 for other reasons .Amniotic fluid puncture and fetal karyotype analysis were carried out for positive on the test results, telephone follow-up after fetus birth for the negative test result. Results ①In 19 out of 1365 pregnant women，massively parallel genomic sequencing technology revealed high risk of Down’s syndrome, 18 had amniotic cavity puncture and chromosome karyotype , 1 high risk fetuses was misdiagnosed .The detection rate of fetal Down’s syndrome was 100％, accurate rate 94.4%. ②Non-invasive technology detected 8 cases of 18 trisomy, 1case refused for puncture , 7 cases consistent with the result of karyotype analysis .③6 cases karyotype were 45,X0, 3 cases in testing positive for the amniotic cavity puncture, 2 cases of karyotype 45, X0, 1 case of 46, XX. ④Providing telephone follow-up for screening negative cases, no Down’s syndrome baby was found. Conclusions Sequencing technology of plasma free DNA in pregnant women can detect fetus chromosome aneuploidy rapidly，and which is highly consistent with karyotype analysis in accuracy and specificity.
