摘要目的:探讨高通量测序技术对于除21、18、13等常见的染色体非整倍体异常外染色体拷贝数变异检测的临床意义。方法:选取自愿参与无创产前检测(non-invasive prenatal test，NIPT)的孕妇37 306例，对NIPT结果提示存在基因组拷贝数变异(copy number variation，CNV)并愿意接受产前诊断的52例孕妇进行羊水穿刺，进行羊水细胞染色体核型分析及染色体微阵列芯片分析(chromosomal microarray analysis ，CMA)，并对所有NIPT提示存在CNV的病例进行随访。结果:在37 306份NIPT样本中共检测到CNV 78例，阳性率为2.09‰。其中52例孕妇行进一步产前诊断，共检出与NIPT结果较一致的拷贝数变异15例，阳性率达28.85%。此外，对未进行诊断的26例孕妇进行了随访，其中自然流产2例，超声提示胎儿结构畸形后选择引产2例，新生儿多发畸形1例(CMA检测结果与NIPT较为一致)，异常率高达19.23%，明显高于正常活产儿的异常率。结论:NIPT提示胎儿拷贝数缺失或重复是胎儿染色体异常的高危指征，联合应用染色体核型分析及CMA技术，可以简便、特异地检出大片段染色体结构异常及CNVs，提高染色体疾病的检出率，为遗传咨询和生育指导提供依据。

abstractsObjective:To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal copy number variations (CNVs) in addition to trisomies 21, 18, and 13.Methods:A total of 37 306 pregnant women underwent the NIPT test. For those with fetal CNVs indicated by NIPT and accepted invasive prenatal diagnosis, amniotic fluid samples were obtained for chromosomal karyotyping analysis and chromosome microarray analysis (CMA). All cases were followed up.Results:Among the 37 306 cases, 78 (2.09‰) were predicted to have fetal CNVs. Among these, 52 pregnant women accepted invasive prenatal diagnosis, and 15 of them (28.85%) obtained a consistent result. Follow up of 26 women who refused invasive prenatal diagnosis have found 2 cases with spontaneous abortion, 2 with induced labor for fetal malformation indicated by ultrasonography, and 1 had multiple malformations and a consistent result by CMA, which yielded an abnormal rate of 19.23%.Conclusion:NIPT can signal fetal chromosomal abnormalities through detection of gain and/or loss of fetal DNA copies. Combined chromosomal karyotyping and CMA can increase the detection rate for common chromosomal aneuploidies and CNVs, thereby provide a basis for genetic counseling for the affected families.