标题：四维彩超结合拷贝数变异诊断胎儿神经系统发育畸形的临床研究

      作者：杨水艳，肖艳华，曾蓓，张明洁    焦作市妇幼保健院孕产保健科，河南 焦作 454000

      卷次： 2023年34卷23期

      【摘要】 目的 研究四维彩超结合拷贝数变异诊断胎儿神经系统发育畸形的临床价值。方法 选取2019年10月至2022年2月在焦作市妇幼保健院进行产前检查的4 150例胎儿作为研究对象，均在孕11~28周进行四维超声检查。在四维超声诊断为胎儿神经系统发育畸形的孕妇知情自愿的基础上，对引产的孕妇采集胎儿大腿内侧皮肤肌肉组织，对有继续妊娠意愿的孕妇行羊水穿刺，进行基因组拷贝数变异测序(CNV-seq)检测和染色体核型分析，并跟踪孕产结局，分析四维彩超结合拷贝数变异(CNV)对胎儿神经系统发育畸形的诊断价值。结果 4 150例胎儿中共有108例最终确诊为胎儿神经系统发育畸形。108例神经系统发育畸形胎儿行染色体核型分析检查，共检出有8例染色体核型异常，检出率为7.41%；108例神经系统发育畸形胎儿行CNV-seq检查结果显示17例异常，其中6例为临床意义不明拷贝数(VOUS)，11例为致病性CNV，检出率为15.74%。8例致病性CNV与染色体核型分析结果一致，其余3例致病性CNV染色体核型分析未检出。结论 四维彩超对胎儿神经系统发育畸形有较好的诊断价值，在此基础上进行CNV-seq能够更加系统全面地找出胎儿神经系统发育畸形的遗传学病因，为孕妇是否继续妊娠提供客观依据，也为再次妊娠提供参考。
      【关键词】 四维彩超；拷贝数变异；胎儿神经系统发育畸形；基因组变异测序
      【中图分类号】 R714.51 【文献标识码】 A 【文章编号】 1003—6350（2023）23—3423—05

Clinical study of four-dimensional color doppler ultrasonography combined with copy number variation in thediagnosis of fetal nervous system developmental malformation.
YANG Shui-yan, XIAO Yan-hua, ZENG Bei, ZHANGMing-jie. Department of Maternal and Child Health Care, Jiaozuo Maternal and Child Health Hospital, Jiaozuo 454000,Henan, CHINA
【Abstract】 Objective To study the clinical value of four-dimensional color doppler ultrasonography combinedwith copy number variation in the diagnosis of fetal nervous system developmental malformation. Methods A total of4 150 fetuses who underwent prenatal examination in Jiaozuo Maternal and Child Health Hospital from October 2019 toFebruary 2022 were selected as the research objects, and all of them underwent four-dimensional ultrasound at 11 to 28weeks of gestation. On the basis of informed consent of pregnant women diagnosed as fetal nervous system developmen-tal malformations by four-dimensional ultrasound, the skin and muscle tissues of the inner thigh of the fetus were collect-ed from the pregnant women with induced labor, and amniocentesis was performed on the pregnant women with the in-tention to continue pregnancy. Genome copy number variation sequencing (CNV-seq) detection and chromosomekaryotype analysis were performed, and the pregnancy outcome was tracked to analyze the diagnostic value offour-dimensional ultrasound combined with copy number variation (CNV) for fetal nervous system developmentalmalformations. Results A total of 108 of the 4 150 fetuses were finally diagnosed as fetal nervous system malforma-tion. Chromosome karyotype analysis was performed in 108 fetuses with developmental malformations of the nervoussystem, and 8 cases of chromosome karyotype abnormalities were detected, with a detection rate of 7.41%. CNV-seq ex-amination of 108 fetuses with developmental malformations of the nervous system revealed 17 abnormalities, of which 6were clinically significant unknown copy numbers (VOUS) and 11 were pathogenic CNV, with a detection rate of15.74%. Eight cases of pathogenic CNV were consistent with the results of karyotype analysis, and the other 3 cases ofpathogenic CNV were not detected by karyotype analysis. Conclusion Four-dimensional color Doppler ultrasound hasa good diagnostic value for fetal nervous system malformation. On this basis, CNV-seq can find out the genetic causes offetal nervous system malformation more systematically and comprehensively, and provide objective basis for pregnantwomen whether to continue pregnancy, and also provide reference for the second pregnancy.
      【Key words】 Four-dimensional color doppler; Copy number variation; Developmental malformation of fetal ner-vous system; Genome variation sequencing