151例高通量测序无创产前筛查高风险胎儿的产前诊断结果分析

摘要

Objective To assess the value of combined fetal karyotyping and chromosomal microarray analysis (CMA) for the verification of high-risk pregnancy signaled by noninvasive prenatal screening (NIPS) based on high-throughput sequencing.Methods One hundred and fifty-one pregnant women with high risks for aneuploidies of chromosomes 13,18,21,X and Y or pathological copy number variations (CNVs) by NIPS were subjected to amniocytic karyotyping and CMA analysis.Results One hundred and forty-two women were found to have a high risk for fetal chromosomal aneuploidies,which included 83 cases of trisomy 21,17 cases of trisomy 18,2 cases of trisomy 13,and 40 cases of sex chromosome aneuploidies.Amniocytic karyotyping and CMA analysis has confirmed 81 cases of trisomy 21,15 cases of trisomy 18,10 cases of 47,XXY,4 cases of 47,XXX,2 cases of 47,XYY and 1 case of 46,X,del (X) (q26.1).Two trisomy 21,two trisomy 18,2 trisomy 13,and 23 cases of sex chromosomal aneuploidies were verified as false positives.For 9 women with pathological fetal CNVs detected by NIPS,combined fetal karyotyping and CMA has confirmed 1 case of chromosome 13 microdeletion,1 case of chromosome 18 microduplication,and 1 case of chromosome 18 deletion.For a case with 30 Mb duplication of chromosome 2 and 25 Mb duplication of chromosome 8,CMA analysis had no positive finding,while fetal umbilical cord blood karyotyping has yielded a 46,XX,dup(2)(p23.1p25.3)[13]/46,XX[87] karyotype.The remaining 5 cases were confirmed as false positive results.Conclusion Combined fetal karyotyping and CMA has provided a powerful tool for verifying high-risk fetuses signaled by NIPS.%目的 评估联合应用胎儿染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA)明确151例高通量测序无创产前筛查(noninvasive prenatal screening,NIPS)提示高风险的病例的临床意义.方法 以高通量测序NIPS提示胎儿13、18、21、性染色体非整倍体高风险以及胎儿染色体拷贝数变异(copy number variations,CNVs)高风险、需进行产前诊断的孕妇为研究对象.在征得知情同意后,经羊膜腔穿刺或脐静脉穿刺获取胎儿细胞,进行染色体核型及CMA分析.结果 在151例胎儿中,有142例为非整倍体高风险,其中21三体高风险83例、18三体高风险17例、13三体高风险2例、性染色体非整倍体高风险40例,经染色体核型和CMA分析确认21三体81例、18三体15例、47,XXY 10例、47,XXX 4例、47,XYY 2例、46,X,del(X)(q26.1)1例,其余2例21三体高风险、2例18三体高风险、2例13三体高风险、23例性染色体非整倍体高风险病例经染色体核型和CMA检测均为46,XN;另外9例高通量测序提示CNVs高风险,其中13号染色体微缺失1例、18号染色体微重复1例、18号染色体部分缺失1例均经CMA证实,1例2号染色体重复30 Mb合并8号染色体重复25 Mb病例CMA未发现拷贝数变异,胎儿脐血染色体核型为46,XX,dup(2)(p23.1p25.3)[13]/46,XX[87],其余5例经检测均未见异常.结论 高通量测序NIPS高风险的胎儿,仍有必要通过介入性产前诊断进行胎儿染色体核型联合CMA分析,以区分真阳性与假阳性的结果.