高通量基因组测序在双胎胎儿染色体非整倍体疾病产前筛查中的应用
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摘要
目的探讨高通量基因组测序在双胎胎儿染色体非整倍体疾病产前筛查中的应用价值。方法选取本院双胎妊娠样本198例,包括自然双胎174例,辅助生殖技术植入的双胎24例,采用无创产前DNA高通量基因组检测,通过Z值≥3进行阴性和阳性判断,对阳性结果进行胎儿羊水穿刺染色体核型分析。结果 198例双胎妊娠样本经高通量基因组测序,检查结果正常者190例,异常者8例,其中21-三体4例,18-三体3例,13-三体1例;其异常染色体对应Z值分别为7.76、5.04、4.98、8.14、7.54、6.53、7.12、7.43,明显高于判定值Z=3。8例异常者进行羊膜腔穿刺术,羊水核型结果显示4例21-三体核型;2例18-三体核型;上述结果与高通量基因组测序结果一致,此6例均选择减胎术;高通量基因组测序结果提示2例异常,分别为1例18-三体高风险、1例13-三体高风险,羊水核型分别为46,XN、46XN,该2例产妇正常分娩,胎儿未见异常;双胎无创产前DNA高通量基因组检测的灵敏度为75.0%、特异度为98.95%、出现假阳性2例,假阳性率为1.01%、未出现假阴性,假阴性率为0.00%。结论双胎无创产前DNA高通量基因组检测在双胎胎儿染色体非整倍体疾病产前筛查中具有较高的灵敏度和特异度,值得在临床上推广应用。
Objective:To investigate the application value of the high-throughput genome sequencing in prenatal screening for aneuploidy in twin pregnancy. Methods:In this study,the data came from 198 cases of twin pregnancies,including 174 natural twin pregnancies,and 24 in vitro fertilization assisted pregnancies. All the cases received the noninvasive prenatal testing for aneuploidy by high-throughput genome sequencing of maternal plasma DNA. The Z score was used to distinguish between normal and abnormal chromosome,fetal karyotyping was also carried out on amniocentesis if the women were judged as high risk.Results:Through the high-throughput genome sequencing,190 cases were negative,and 8 cases were positive,including 4 cases of 21-trisomy syndrome,3 cases of 18-trisomy syndrome,and 3 cases of 13-trisomy syndrome(Z=7.76,5.04,4.98,8.14,7.54,6.53,7.12,7.43>3);Amniocentesis was performed in 8 cases with abnormalities. Amniotic fluid karyotype results showed 4 cases of 21-trisomy karyotype;2 cases of 18-trisomy karyotype;the above results and high-throughput genome Sequencing results are consistent,6 cases were selected to reduce the fetus;The results of high-throughput genomic sequencing suggested that 2 cases were abnormal,1 case of 18-trisomy high risk,1 case of 13-trisomy high risk,amniotic fluid karyotype46,XN,46 XN,respectively.The two cases of maternal normal delivery,the fetus is not abnormal. High-throughput genome sequencing had a sensitivity of 75.0% and a specificity of 98.95% with a false positive rate of 1.01%(2 cases)and a false negative rate of 0.00%. Conclusion:Non-invasive prenatal DNA high-throughput genomic detection has high sensitivity and specificity in prenatal screening for twin aneuploidy chromosomal aneuploidies,and is worthy of clinical application.
Objective:To investigate the application value of the high-throughput genome sequencing in prenatal screening for aneuploidy in twin pregnancy. Methods:In this study,the data came from 198 cases of twin pregnancies,including 174 natural twin pregnancies,and 24 in vitro fertilization assisted pregnancies. All the cases received the noninvasive prenatal testing for aneuploidy by high-throughput genome sequencing of maternal plasma DNA. The Z score was used to distinguish between normal and abnormal chromosome,fetal karyotyping was also carried out on amniocentesis if the women were judged as high risk.Results:Through the high-throughput genome sequencing,190 cases were negative,and 8 cases were positive,including 4 cases of 21-trisomy syndrome,3 cases of 18-trisomy syndrome,and 3 cases of 13-trisomy syndrome(Z=7.76,5.04,4.98,8.14,7.54,6.53,7.12,7.43>3);Amniocentesis was performed in 8 cases with abnormalities. Amniotic fluid karyotype results showed 4 cases of 21-trisomy karyotype;2 cases of 18-trisomy karyotype;the above results and high-throughput genome Sequencing results are consistent,6 cases were selected to reduce the fetus;The results of high-throughput genomic sequencing suggested that 2 cases were abnormal,1 case of 18-trisomy high risk,1 case of 13-trisomy high risk,amniotic fluid karyotype46,XN,46 XN,respectively.The two cases of maternal normal delivery,the fetus is not abnormal. High-throughput genome sequencing had a sensitivity of 75.0% and a specificity of 98.95% with a false positive rate of 1.01%(2 cases)and a false negative rate of 0.00%. Conclusion:Non-invasive prenatal DNA high-throughput genomic detection has high sensitivity and specificity in prenatal screening for twin aneuploidy chromosomal aneuploidies,and is worthy of clinical application.
引文
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[15]殷一旋.无创产前基因检测及羊水产前诊断在高龄孕妇中的对照研究分析[J].中国优生与遗传杂志,2017,6(3):23-24.
[16]曾筱凡,赵文瑞,康辉,等.无创产前基因检测之政策与伦理分析[J].中国医学伦理学,2017,30(5):556-559.
[17]Walker R,Llewellyn A,Harden M,et al."High-throughput,non-invasive prenatal testing for fetal rhesus D status in RhDnegative women:a systematic review and meta-analysis"[J]. Bmc Medicine,2017,7(4):45-48.
[18]加秋萍.无创产前基因检测在胎儿染色体非整倍体产前筛查中的应用价值[J].中国妇幼保健,2017,32(17):4203-4205
[2]谢建渝,等.产前无创基因检测在诊断胎儿染色体非整倍体疾病中的临床价值[J].检验医学与临床,2017,14(24):34-35.
[3]姚静怡,崔岚,岳胜,等.双胎妊娠胎儿染色体非整倍体产前筛查的研究进展[J].国际妇产科学杂志,2017,44(1):67-70.
[4]Gandhi H. OP22.06:Changing trend in common chromosomal aneuploidy management in the United Kingdom[J]. Ultrasound in Obstetrics&Gynecology,2017,50(3):230-232.
[5]Badeau M,Lindsay C,Blais J,et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women[J]. Cochrane Database of Systematic Reviews,2017,11(7):767-769.
[6]王亚男,赵柏丽. NIPT-plus在产前筛查中的应用研究[J].中国优生与遗传杂志,2017,54(9):60-61.
[7]Lei T,et al. Chromosomal Aneuploidies and Copy Number Variations in Posterior Fossa Abnormalities Diagnosed by Prenatal Ultrasonography.[J]. Prenatal Diagnosis,2017,34(3):23-25.
[8]Reiss RE,et al. Sex Chromosome Aneuploidy Detection by NonInvasive Prenatal Testing:Helpful or Hazardous?[J]. Obstetrical&Gynecological Survey,2017,72(5):583-585.
[9]陈晨,朱朝锋,等.胎儿游离DNA在染色体非整倍体疾病无创产前筛查中的应用[J].中国优生与遗传杂志,2017,7(2):26-28.
[10]Calcagni G,et al. Congenital heart disease and genetic syndromes:new insights into molecular mechanisms[J]. Expert Review of Molecular Diagnostics,2017,17(9):861-870.
[11]鲍幼维,等.无创DNA检测技术在产前胎儿非整倍体筛查中的应用[J].中国优生与遗传杂志,2017,6(6):38-39.
[12]Zhu L,Cheng J,Zhou B,et al. Diagnosis for choroideremia in a large Chinese pedigree by next-generation sequencing(NGS)and non-invasive prenatal testing(NIPT)[J]. Molecular Medicine Reports,2017,15(3):1157-1164.
[13]侯亚萍,杨洁霞,郭芳芳,等.广东地区6668例孕妇无创DNA产前检测结果分析[J].中国妇幼保健,2017,32(6):1241-1244.
[14]Druais S,Sambuc C,et al. Costs and Benefits of Implementing Non-Invasive Prenatal Testing For Trisomy 21(T21)Based on Cell Free DNA(CFDNA)Sequencing In Maternal Plasma In France[J]. Value in Health,2017,20(9):A721-A722.
[15]殷一旋.无创产前基因检测及羊水产前诊断在高龄孕妇中的对照研究分析[J].中国优生与遗传杂志,2017,6(3):23-24.
[16]曾筱凡,赵文瑞,康辉,等.无创产前基因检测之政策与伦理分析[J].中国医学伦理学,2017,30(5):556-559.
[17]Walker R,Llewellyn A,Harden M,et al."High-throughput,non-invasive prenatal testing for fetal rhesus D status in RhDnegative women:a systematic review and meta-analysis"[J]. Bmc Medicine,2017,7(4):45-48.
[18]加秋萍.无创产前基因检测在胎儿染色体非整倍体产前筛查中的应用价值[J].中国妇幼保健,2017,32(17):4203-4205
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