5997例母血胎儿游离DNA无创大规模平行测序筛查胎儿染色体数目异常  

Non-invasive screening for chromosome abnormality in fetal free DNAs by massively parallel sequencing: report of 5 997 pregnant mothers

作　　者：章容[1] 徐聚春[1] 许欢欢[1] 胡斌[1] 董艳玲[1] 胡华[1] 李俊男[1] 姚宏[1] 

机构地区：[1]第三军医大学西南医院妇产科,产前诊断中心,重庆400038

出　　处：《第三军医大学学报》2013年第16期1744-1747,共4页Journal of Third Military Medical University

摘　　要：目的对比观察母血胎儿游离DNA大规模平行测序(massively parallel sequencing,MPS)无创筛查对常见染色体数目异常的检测能力。方法 2011年6月至2012年11月在第三军医大学西南医院产前诊断中心共募集5 997例孕妇参与本项研究,年龄18～46岁,孕周12～36周。抽取孕妇静脉血5 mL,分离胎儿游离DNA,常规Barcoding建库,Illu-mina GAⅡx测序,测序片段用基于二元假设的t检验和L-score分析。测序提示异常患者进行传统核型分析确认。结果5 997例患者,母血胎儿游离DNA MPS提示染色体异常患者113例。提示异常的患者有89例做了核型对比分析,21-三体符合率100%(28/28),18-三体符合率87.5%(7/8),性染色体异常符合率33.3%(14/42)。传统唐氏综合征筛查对21-三体的漏检率为11.8%(2/17),而MPS方法无一漏检。年龄(P=0.261)和孕周(P=0.309)对MPS的异常检出率没有显著影响。结论无创MPS检测对21-三体筛查的准确性和可信度高,优于传统唐氏综合征筛查方法,适用于21-三体胎儿的产前初筛,以降低羊水/脐血穿刺有创检测比例。Objective To evaluate the detection rate of massively parallel sequencing （MPS） -based screening for chromosome abnormality of fetus free DNAs in their mother＇ s plasma, and provide clinical data for this non-invasive prenatal screening. Methods A total of 5 997 pregnant women with an age from 18 to 46 and a gestational age from 12 to 36 weeks who receiving prenatal examination in our center from June 2011 to November 2012 were recruited in this study. Five milliliters of peripheral blood were collected, and then the fetus DNAs were extracted from mother plasma and barcoded. The libraries of each sample were pooled and subjected to Illumina GA 11 x analyzer. Short reads were analyzed by binary hypothesized t tests and L-score analysis. Pos- itive results of MPS were validated by cordocentesis based karyotyping. Results A total of 113 patients were found to be abnormal by MPS. Among them, 89 mothers accepted cordocentesis based karyotyping, and the obtained sensitivity for trisomy 21 and trisomy 18 were 100% （28/28） and 87.5% （7/8） , respectively. However, the sensitivity for sex chromosome abnormality was 33.3% （14/42）. Routine screening for Down＇ s syndrome showed a false negative ratio of 11.8% （2/17）, while MPS had no false ratio. The age （P =0. 261 ） and gestational weeks （P = 0. 309） had no significant effect on the detection rates of MPS. Conclusion Noninvasive MPS screening is a more reliable detection for trisomy 21 than conventional routine screening for Down＇ s syndrome, and is suitable for large-scale screening for trisomy 21 to reduce the ratio of invasive cordocentesis based karyotyping.

关 键 词：产前诊断 染色体病 核型 大规模平行测序 

分 类 号：R596.1[医药卫生—内科学] R714.55[医药卫生—临床医学]