目的 探讨高通量测序平台的无创基因检测技术应用于产前诊断的可行性。方法 选择2012年4月到2013年5月在广东省妇幼保健院产前诊断中心就诊,孕龄12～32周的3711例单胎妊娠高危孕妇,记录临床指征、年龄、孕周等数据。采用高通量测序平台的无创产前基因检测技术对其外周血游离胎儿DNA进行分析。检测结果为高危的孕妇行羊膜腔穿刺或脐血穿刺术进行胎儿染色体核型分析。结果 3711例孕妇中游离胎儿DNA高通量基因测序技术检测出74例染色体高风险胎儿，羊水／脐血核型分析证实其中131例为染色体异常，分别为43例21-三体和10例18-三体，6例13-三体，7例性染色异常，8例其它常染色异常（分别为16号染色体微缺失和22号环状染色体），1例21-三体和6例其它染色体异常证实为假阳性。结论 利用高通量测序平台的无创产前基因检测技术可快速、准确地检测出胎儿13、18、21染色体非整倍体异常，其敏感性、特异性与染色体核型分析技术具有较高的一致性。但是对于其他染色体异常准确性还有待技术完善来进一步提高，对于染色体微缺失、微重复的检测也日益受到众多专家学者的关注，这也是我们以后研究的方向之一。
Objective Using massively parallel genome sequencing technology to detect pregnant women free DNA in peripheral blood plasma,for fetal chromosomal aneuploidy noninvasive prenatal genetic testing, explore aneuploid noninvasive prenatal genetic testing in the value of prenatal screening and prenatal diagnosis. Method From February 2012 to May 2013, a total of 3711 high-risk pregnant women were recruited at Prenatal Diagnostics Center of Guang dong Province MCH，with gestational age from 12 to 34 weeks. Five milliliters of peripheral blood were drawn, the DNA were extracted from mother plasma and barcoded, And test results of high risk which accepted interventional prenatal diagnosis as fetal amniotic fluid or cord blood that is collected by the cell culture underwent karyotype analysis or array-CGH identified chromosome aneuploidy.And all detected pregnant women after childbirth were followed-up. Results 3711 cases of pregnant women with a high risk of blood were 74 cases, including 21 - trisomy 43 cases; 18 - trisomy 10 cases, 13 - trisomy 6 cases, sex chromosome abnormalities in 7 cases, other chromosomal abnormalities 8 cases. Combined the results of Interventional prenatal diagnosis and followed-up, Detection rate of this method for 21-trisomy(40/41)、18-trisomy(8/8)、13-trisomy(4/4) reach 100%,the misdiagnosis rate is 1.08%; sex chromosome detection rate and other chromosome detection rate of 100% (6/6), the misdiagnosis rate of 2.43%. Conclusions Using non-invasive prenatal genetic testing to detect maternal blood plasma of free fetal chromosomal DNA lines aneuploidy screening for 21 - trisomy 、18 - trisomy and 13 – trisomy , the sensitivity, specificity and chromosomal karyotyping have high consistency. But for the sex chromosomes and other chromosomal abnormalities often have some limitations, but also need more data accumulate. The technology has the non-invasive, high accuracy, high throughput advantages in clinical which have considerable potential value.
