摘要
目的探讨基于胎儿游离DNA的基础性与拓展性无创产前检测(noninvasive prenatal testing,NIPT)在胎儿非整倍体异常及染色体拷贝数目变异(copy number variations,CNVs)筛查中的应用价值。方法对2777例基础性与拓展性NIPT检测结果进行回顾,随访妊娠结局,分析孕妇的临床数据、高风险孕妇的产前诊断率、筛查效能。结果2777例孕妇中,42.9%(1192/2777)选择了基础性NIPT,57.1%(1585/2777)选择了拓展性NIPT,失败率为0.1%(3/2777)。共检出21三体高风险8例,性染色体高风险6例,目标疾病外高风险32例。NIPT对21三体高风险阳性预测值为85.7%;拓展性NIPT对性染色体异常的筛查阳性率为0.38%,3例高风险病例进行了产前诊断,确诊47,XXX一例,假阳性2例。对于检测范围外的额外发现,基础性和拓展性NIPT的产前诊断率分别为71.4%(5/7)和68.2%(15/22),确诊7例真阳性CNVs,包括致病性和可疑致病性CNVs各1例,临床意义不明CNVs 5例。6例母源CNVs高风险病例中,5例胎儿携带相应CNVs且母亲为携带者;1例胎儿染色体微阵列分析结果未见异常,但其母亲为相应CNVs携带者。结论NIPT对21三体综合征和母源性CNVs具有较高的阳性预测值,对胎源性CNVs的检测效能有限。检测前由孕妇知情选择是否获知目标疾病外的高风险结果是NIPT临床应用的可选方案,目标疾病外的高风险病例可结合胎儿超声筛查结果选择是否行介入性产前诊断,但需充分告知可能的残余风险。
Objective To assess the application value of noninvasive prenatal testing(NIPT)based on cell-free fetal DNA.Methods The results of 2777 cases of basic and extended NIPT were retrospectively analyzed.The clinical data and outcome of pregnancy were analyzed,in addition with the diagnosis rate and testing efficiency.Results Among the 2777 pregnant women,1192(42.9%)had accepted basic NIPT and 1585(57.1%)accepted extended NIPT.With a failure rate of 0.1%,8 and 6 cases were reported respectively as high-risk pregnancies for trisomy 21 and sex chromosomal abnormalities.Other genetic abnormalities were detected in 32 cases.The positive predictive value for trisomy 21 was 85.7%,and one case of 47,XXX was diagnosed among 3 women with high risks for sex chromosomal abnormalities.For those with a high risk for other genetic abnormalities,pregnant diagnosis rates of basic and extended NIPT were 71.4%(5/7)and 68.2%(15/22),respectively.Seven copy number variations(CNVs)were confirmed,including one pathogenic CNV,one likely pathogenic CNV and 5 variants of unknown significance.Among 6 cases with high-risk of maternal CNVs,5 fetuses and the mothers were confirmed to be carriers.No CNV was detected in the remainder fetus by chromosomal microarray analysis,while its mother was a carrier of the corresponding CNV.Conclusion NIPT has shown a relatively high positive predictive value for the screening of trisomy 21 and maternal CNVs but with a limited efficiency for the discovery of fetal CNVs.For other genetic abnormalities signaled by NIPT,informed choice by the pregnant women during pre-testing consultation is recommended.Invasive prenatal diagnosis should be considered in the combination of NIPT reports and fetal ultrasound,while the residual risks should be fully informed.
作者
段红蕾
王皖骏
张颖
刘威
顾雷雷
李洁
Duan Honglei;Wang Wanjun;Zhang Ying;Liu Wei;Gu Leilei;Li Jie(Center of Prenatal Diagnosis,Department of Obstetrics and Gynecology,Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School,Nanjing,Jiangsu 210008,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第3期264-268,共5页
Chinese Journal of Medical Genetics
基金
江苏省妇幼健康科研项目(F202118)
南京市卫生科技发展专项(YKK21096)。
关键词
胎儿游离DNA
无创产前筛查
产前诊断
假阳性率
阳性预测值
Cell-free fetal DNA
Noninvasive prenatal testing
Prenatal diagnosis
False positive rate
Positive predictive value
