拷贝数变异测序与染色体核型分析在产前诊断应用中的比较研究

Study of the application of copy number variation sequencing and traditional karyotyping in prenatal diagnosis

目的探讨拷贝数变异测序技术在产前诊断胎儿染色体病的临床应用价值。方法对具有产前诊断指征的孕妇知情同意抽取胎儿羊水样本进行胎儿染色体核型分析和拷贝数变异测序检测(copy number variant sequencing,CNV-Seq),评价CNV-Seq技术在产前诊断中对胎儿染色体病的检测效能。结果在434例产前诊断病例中共有43例核型分析能够检出的染色体数目异常胎儿和1例del15q11.2微缺失综合征胎儿,CNV-Seq检出了其中的42例染色体数目异常(包括1例45,X[25]/46,XY[18]嵌合体和1例45,X[55]/46,X,+mar[5]嵌合体)和1例核型分析技术未能检出的del15q11.2微缺失综合征,但有1例45,X[5]/46,XX[45]的嵌合体Turner综合征被CNV-Seq漏检;CNV-Seq的报告时限缩短到平均7个工作日,而羊水细胞培养核型分析的报告时限是平均21个工作日。结论 CNV-Seq和核型分析技术联合应用于产前诊断,可提高产前诊断对染色体病,特别是对微缺失/微重复综合征的检出能力,缩短产前诊断报告时限,进一步提高了严重出生缺陷的预防能力。

Objective To explore the clinical application value of copy number variation sequencing in prenatal diagnosis of fetal chromosomal diseases.Methods After the informed consent of pregnant women with prenatal diagnosis indications,amniocentesis were performed for fetal karyotyping and copy number variation sequencing to evaluate the effectiveness of CNV-Seq in detecting fetal chromosomal diseases in prenatal diagnosis.Results A total of 43 fetuses with chromosome aneuploidy detected by karyotyping and one fetus with 15 q11.2 microdeletion syndrome were diagnosed among 434 prenatal diagnosis cases.CNV-Seq detected 42 cases of chromosome aneuploidy(including 1 case of 45,X[25]/46,XY[18]mosaic and one case of 45,X[55]/46,X,+mar[5] chimera) and one case of 15 q11.2 microdeletion syndrome that could not be detected by karyotyping,but one case of 45,X[5]/46,XX[45] chimera Turner syndrome was missed by CNV-Seq.The reporting time of CNV-Seq was shortened to an average of 7 working days,while the karyotyping reports after amniotic fluid cell culture costed almost 21 working days.Conclusion The combined application of CNV-Seq and karyotyping in prenatal diagnosis would be a better model for prenatal diagnosis to detect chromosomal diseases,especially the microdeletion/microduplication syndrome.It may shorten the time of prenatal diagnosis reporting and improve our ability to prevent serious birth defects.