Objective: To explore the practical application value of high-throughput sequencing (also known as next generation sequencing) whole genome copy number variations (NGS-CNVs) in prenatal diagnosis in comparison with chromosomal karyotype analysis of amniotic fluid cells. Methods: From January 2017 to December 2019, pregnant women with indications of prenatal diagnosisin our hospital were recruited. Amniotic fluid samples were obtained by aseptic amniocentesis and then amniotic fluid cells were collected to perform the NGS-CNVs and chromosome karyotype analysis, thereby verifying the feasibility of NGS-CNVs in prenatal diagnosis.Results: Among 201 amniotic fluid samples, 6 cases (2.99%) of abnormal chromosome number and 1 case (0.50%) of abnormal chromosome structure were detected by two methods. NGS-CNVs technology also verified another 2 cases of pathogenic CNVs, 6 cases of polymorphism and 6 cases of clinically unknown CNVs, while no chromosomal abnormalities in the corresponding amniotic fluid cells were detected by chromosome karyotype analysis. Simultaneously, chromosome karyotype analysis also revealed another 7 cases of balanced translocation, 5 cases of interarm inversion and 6 cases of chromosome polymorphism, but no changes of CNVs in the corresponding amniotic fluid cells were detected by NGS-CNVs technology. Although the rate of abnormal chromosomes detected by NGS-CNVs technology was slightly lower than that by chromosome karyotype analysis, McNemar statistical analysis showed that the two methods were consistent in the diagnosis of chromosomal abnormalities(P=0.597).Conclusion: NGS-CNVs technique is helpful to make up for the defects in the low resolution of chromosome karyotype analysis, improve the level of prenatal genetic examination and reduce birth defects, but it cannot completely replace chromosome karyotype analysis. |
[1] 关蔚, 钱梦岑, 李小攀, 等.2015~2017年上海市某医院新生儿出生缺陷流行病学特征分析[J].生殖医学杂志, 2020, 29(1):68-72.
[2] American College of Obstetricians and Gynecologists Committee on Genetics.Committee opinion no.581:the use of chromosomal microarray analysis in prenatal diagnosis[J].Obstet Gynecol, 2013, 122(6):1374-1377.
[3] CHEN L, ZHOU W, ZHANG L, et al.Genome architecture and its roles in human copy number variation[J].Genomics Inform, 2014, 12(4):136-144.
[4] 姜楠, 张印帅, 宋丽杰, 等.高通量测序技术在胎儿染色体拷贝数变异检测中的应用[J].中华医学遗传学杂志, 2020, 37(7):779-784.
[5] HUI L, POULTON A, KLUCKOW E, et al.Population-based prevalence of 22q11 deletion syndrome and other chromosome abnormalities in a combined prenatal and postnatal cohort[J].Ultrasound Obstet Gynecol, 2019, 54(S1):14-15.
[6] 卢建, 李星, 黄伟伟, 等.染色体微阵列分析技术在新生儿出生缺陷中的应用[J].中华实用儿科临床杂志, 2019, 34(16):1231-1233.
[7] 魏友华, 朱文娟, 张延霞, 等.高通量基因测序检测染色体拷贝数变异与染色体核型分析在产前诊断中联合应用的价值[J].中华医学遗传学杂志, 2020, 37(10):1191-1193.
[8] 湃孜莱提·哈斯木, 夏燕, 叶尔登切克, 等.高通量测序技术在介入性产前诊断中的应用[J].中国优生与遗传性杂志, 2019, 27(6):674-675.
[9] 何冰, 黄莉, 张鹏, 等.羊水细胞高通量测序与染色体核型分析在产前诊断中的应用研究[J].中国临床新医学, 2015, 12(8):1113-1116.
[10] 戚桂杰, 易建平, 王思, 等.基因拷贝数变异检测在308例羊水细胞中的临床应用[J].中国优生与遗传性杂志, 2019, 27(6):671-673.
[11] LOVRECIC L, REMEC Z I, VOLK M, et al.Clinical utility of array comparative genomic hybridization in prenatal setting[J].BMC Med Genet, 2016, 17(1):81.
[12] KASHEVAROVA A A, SKRYANBIN N A, NIKITINA T V, et al.Ontogenetic pleiotropy of genes involved in CNVs in human spontaneous abortions[J].Russ J Genet, 2019, 55(10):1214-1226.
[13] VANSTONE M, CERNAT A, NISKER J, et al.Women's perspectives on the ethical implications of non-invasive prenatal testing:a qualitative analysis to inform health policy decisions[J].BMC Med Ethics, 2018, 19(1):27.
[14] 王念, 林立, 周燕虹, 等.中国西南地区6907例外周血染色体核型分析[J].现代医学, 2020, 48(9):1185-1190.
[15] 张影, 向卉芬, 徐祖滢, 等.高通量测序技术在复发性流产病因诊断中的应用[J].中华生殖与避孕杂志, 2018, 38(2):127-130. |
