孕妇血浆游离胎儿DNA检测在产前诊断中的应用

Application of detecting free DNA from maternal plasma for fetal chromosomal aneuploidies in prenatal diagnosis

目的:介绍孕妇血浆中游离胎儿DNA高通量基因测序技术在非创伤性产前诊断中的应用现状,探讨其存在的优缺点及可行性。方法:收集3 695例在本院门诊做孕中期产前诊断的孕妇血浆,采用高通量基因测序技术检测母体血浆胎儿游离DNA,分析胎儿染色体拷贝数;对筛查高危孕妇行羊膜腔穿刺及脐血穿刺术进行胎儿染色体核型分析。结果:孕妇血浆中游离胎儿DNA高通量基因测序技术共检测出39例染色体高风险胎儿,2例可疑高风险胎儿,经羊水/脐血核型分析证实其中39例为染色体异常,分别为31例21-三体和7例18-三体,1例13-三体。游离胎儿DNA高通量基因测序技术的敏感度为100.0%,特异度为99.9%。结论:母体血浆游离DNA高通量基因测序技术可用于筛查胎儿染色体拷贝数异常的检测,但仍然需要与传统染色体分析技术结合做产前诊断。

Objective To investigate the application of non-invasive prenatal diagnosis in prenatal screening by high-flux sequencing analysis of free fetal DNA from maternal plasma, and discuss the feasibility and value in clinical procedure. Methods High-flux sequencing was applied to analyze fetal chromosome sequence copy numbers in 3 695 pregnant women in outpatient of our hospital. Fetal karyotyping was also carried out on amniocentesis samples or puncture of umbilical cord samples with those high risk pregnant women. Results 39 cases were detected with fetal chromosomal abnormalities by high-flux sequencing analysis and 2 cases were suspicious high risk ones. Among these cases, 39 were confirmed by karyotyping to be chromosomal aneuploidies, including 31 cases of 21 trisomy, 7 cases of 18 trisomy and 1 case of 13 trisomy. The sensitivity and specificity of high-flux sequencing were 100%（39/39） and 99.9%（3654/3656）, respectively. Conclusion High-flux sequencing analysis of free fetal DNA from maternal plasma is efficient for detecting fetal chromosomal aneuploidies. However, it still needs to combine with traditional chromosome analysis to make the final conclusion.