3164例高龄孕妇NIPT检测胎儿染色体的应用探讨
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摘要
目的探讨NIPT技术在高龄孕妇产前检测胎儿染色体非整倍体异常中的应用价值。方法利用高通量测序技术检测高龄孕妇外周血中胎儿游离DNA(cffDNA),结合生物学信息分析,提示染色体异常者行羊膜腔穿刺术,进行羊水细胞培养及染色体核型分析,再对比NIPT结果和染色体核型分析结果。结果 (1)NIPT高风险者63例:其中26例21-三体高风险;4例18-三体高风险;3例13-三体高风险;30例性染色体异常(21例ChrX-;2例ChrY+,7例ChrX+/Y+)。(2)63例NIPT高风险孕妇中,3例性染色体异常(ChrX-)拒绝羊水穿刺检测要求继续妊娠;其余60例进一步行羊水穿刺产前诊断,最终确诊胎儿染色体异常者45例(21-三体25例;18-三体3例;13-三体0例;45,X10例;47,XXY/XXX5例,47,XYY2例);余15例NIPT异常羊水穿刺结果未见异常(1例21-三体高风险;1例18-三体高风险;3例13-三体高风险;8例ChrX-;2例ChrX+/Y+)。(3)NIPT技术应用于高龄孕妇对21-三体符合率较高,达96.2%;18-三体的符合率为75%;但对13-三体符合率为0。在性染色体非整倍体检测中,NIPT对核型为47,XYY和47,XXX/XXY符合率较高,达100%和71.4%;但对45,X的符合率仅为55.56%。结论 NIPT应用于高龄孕妇产前检测,对胎儿21-三体符合率较高,对18-三体符合率也较高;但对13-三体符合率较低;对胎儿性染色体异常符合率差异较大,47,XYY和47,XXX/XXY符合率较高,但对45,X符合率偏低。NIPT结果异常的孕妇仍需进一步羊水穿刺确诊,避免不必要的引产。
Objective:To explore the value of NIPT technique in prenatal detection of fetal chromosomal aneuploidy in elderly pregnant women.Methods:High-throughput sequencing technique was used to detect fetal free DNA(cffDNA)in peripheral blood of elderly pregnant women.Combined with the analysis of biological information,amniocentesis was performed for those with chromosomal abnormalities,amniotic fluid cell culture and karyotype analysis were performed.The results of NIPT and karyotype analysis were compared.Results:(1)There were 63 cases with high risk of NIPT,including 26 cases with high risk of 21-trisomy,4 cases with high risk of 18-trisomy,3 cases with high risk of 13-trisomy,and 30 cases with abnormal sex chromosome(21 cases with ChrX-,2 cases with ChrY+,7 cases with ChrX+/Y+).(2)Among 63 high-risk pregnant women with NIPT,3 had sex chromosome abnormalities(ChrX-)who refused amniocentesis for further pregnancy;the remaining 60 had further amniocentesis for prenatal diagnosis,and the final diagnosis of fetal chromosomal abnormalities was 45(21-trisomy 25cases;18-trisomy 3 cases;13-trisomy 0 cases;45,X 10 cases;47,XXY/XXX 5 cases,47,XYY 2 cases).The other 15 cases of NIPT abnormal amniocentesis results were not abnormal(1 case 21-trisomy high risk;1 case 18-trisomy high risk;3 cases 13-trisomy high risk;8 cases ChrX-;2 cases ChrX+/Y+).(3)The coincidence rate of NIPT with trisomy 21 was 96.2%,that of trisomy 18 was 75%,but that of trisomy 13 was 0.In the detection of sex chromosome aneuploidy,the coincidence rate of NIPT pairs with karyotypes 47,XYY and 47,XXX/XXY was 100% and 71.4%,but only 55.56% for 45 and X.Conclusion:NIPT has a high coincidence rate for fetal trisomy 21 and trisomy 18,but a low coincidence rate for trisomy 13 and a high coincidence rate for fetal sex chromosome 47,XYY and 47,XXX/XXY,but a low coincidence rate for 45 and X.Pregnant women with abnormal NIPT results still need further amniocentesis to avoid unnecessary labor induction.
Objective:To explore the value of NIPT technique in prenatal detection of fetal chromosomal aneuploidy in elderly pregnant women.Methods:High-throughput sequencing technique was used to detect fetal free DNA(cffDNA)in peripheral blood of elderly pregnant women.Combined with the analysis of biological information,amniocentesis was performed for those with chromosomal abnormalities,amniotic fluid cell culture and karyotype analysis were performed.The results of NIPT and karyotype analysis were compared.Results:(1)There were 63 cases with high risk of NIPT,including 26 cases with high risk of 21-trisomy,4 cases with high risk of 18-trisomy,3 cases with high risk of 13-trisomy,and 30 cases with abnormal sex chromosome(21 cases with ChrX-,2 cases with ChrY+,7 cases with ChrX+/Y+).(2)Among 63 high-risk pregnant women with NIPT,3 had sex chromosome abnormalities(ChrX-)who refused amniocentesis for further pregnancy;the remaining 60 had further amniocentesis for prenatal diagnosis,and the final diagnosis of fetal chromosomal abnormalities was 45(21-trisomy 25cases;18-trisomy 3 cases;13-trisomy 0 cases;45,X 10 cases;47,XXY/XXX 5 cases,47,XYY 2 cases).The other 15 cases of NIPT abnormal amniocentesis results were not abnormal(1 case 21-trisomy high risk;1 case 18-trisomy high risk;3 cases 13-trisomy high risk;8 cases ChrX-;2 cases ChrX+/Y+).(3)The coincidence rate of NIPT with trisomy 21 was 96.2%,that of trisomy 18 was 75%,but that of trisomy 13 was 0.In the detection of sex chromosome aneuploidy,the coincidence rate of NIPT pairs with karyotypes 47,XYY and 47,XXX/XXY was 100% and 71.4%,but only 55.56% for 45 and X.Conclusion:NIPT has a high coincidence rate for fetal trisomy 21 and trisomy 18,but a low coincidence rate for trisomy 13 and a high coincidence rate for fetal sex chromosome 47,XYY and 47,XXX/XXY,but a low coincidence rate for 45 and X.Pregnant women with abnormal NIPT results still need further amniocentesis to avoid unnecessary labor induction.
引文
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[4]Wang Y,Zhu J,Chen Y,et al.Two cases of placental T21mosaicism:challcnging the detection limits of non-invasive prenatal testing[J].Prenat Diagn,2013,33(12):1207-1210.
[5]Lau TK,Jiang FM,Stevenson RJ,et al.Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service[J].Prenat Diagn,2013,33:602-608.
[6]Sehnert AJ,Rhees B,Comstock D,et al.Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood.[J].Clin Chem,2011,57:1042-1049.
[7]Amant F,Verheecke M,Wlodarska I,et al.Presymptomatic identification of cancers in pregnant women during noninvasive prenatal testing[J].JAMA,Oncol,2015,1:814-819.
[8]Mazloom AR,Dzakula Z,Oeth P,et al.Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma[J].Prenat Diagn,2013,33(6):591-597.
[9]Bischoff FZ,Lewis DE,Sinpson JL.Cell-free fetal DNA in maternal blood:Kinetics,source and structure[J].Hum Reprod Update,2015,11(1):59-67.
[10]Russell LM,Strike P,Browne CE,et al.X chromosome loss and ageing[J].Cytogenetic and Genome Research,2007,116(3):181-185.
[2]Alberry M,Maddocks D,Jones M,et al.Free fetal DNA in maternal plasma in anembryonic pregnancies:confirmation that the origin is the trophoblast[J].Prenatal Diagnosis,2007,27(5):415-418.
[3]Gao Y,Stejskal D,Jiang F,et al.False-negative trisomy 18non-invasive prenatal test result due to 48,XXX,+18 placental mosaicism[J].Ultrasound Obstet Gynecol,2014,43:477-478.
[4]Wang Y,Zhu J,Chen Y,et al.Two cases of placental T21mosaicism:challcnging the detection limits of non-invasive prenatal testing[J].Prenat Diagn,2013,33(12):1207-1210.
[5]Lau TK,Jiang FM,Stevenson RJ,et al.Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service[J].Prenat Diagn,2013,33:602-608.
[6]Sehnert AJ,Rhees B,Comstock D,et al.Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood.[J].Clin Chem,2011,57:1042-1049.
[7]Amant F,Verheecke M,Wlodarska I,et al.Presymptomatic identification of cancers in pregnant women during noninvasive prenatal testing[J].JAMA,Oncol,2015,1:814-819.
[8]Mazloom AR,Dzakula Z,Oeth P,et al.Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma[J].Prenat Diagn,2013,33(6):591-597.
[9]Bischoff FZ,Lewis DE,Sinpson JL.Cell-free fetal DNA in maternal blood:Kinetics,source and structure[J].Hum Reprod Update,2015,11(1):59-67.
[10]Russell LM,Strike P,Browne CE,et al.X chromosome loss and ageing[J].Cytogenetic and Genome Research,2007,116(3):181-185.