目的 探讨核型分析和染色体微阵列技术(CMA)在超声软指标异常胎儿产前诊断中的应用。方法 选取同时行核型分析和CMA检测的345例中孕期软指标异常但无明确结构畸形的单胎孕妇,对检测结果和孕妇资料进行分析。结果 345例孕妇软指标异常的病例中,孤立单项软指标152例,合并其他产前指征149例,两项及以上软指标44例,致病性染色体异常检出率分别为2.63%(4/152)、10.74%(16/149)、20.45%(9/44),3组检出率差异有统计学意义(χ²=15.932,P<0.001)。不同软指标的致病性染色体异常检出率为0.00%~21.43%,颈背部皮肤皱褶(NF ) 增厚最高(21.43%),其次是鼻骨缺失/发育不良(12.68%)。345例病例中,核型分析染色体异常检出率为7.25%(25/345),CMA检出率为14.49%(50/345);4例核型异常CMA未检出异常;CMA在核型正常病例中检出29例基因组拷贝数变异(CNV)。结论 NF增厚、鼻骨缺失/发育不良、两项及以上软指标异常或软指标合并其他产前指征胎儿有较高的致病性染色体异常检出率,建议行介入性产前诊断;核型分析和CMA的检测结果可以互相验证补充,两者结合可提供更加准确和有效的遗传学诊断。

Objective To explore the clinical application value of karyotyping and chromosome microarray analysis (CMA) in prenatal diagnosis of fetuses with abnormal ultrasonographic soft markers (USM). Methods A total of 345 singleton pregnant women with abnormal USM but without structural abnormalities who had both karyotyping and CMA testing were selected.Then,the test results and maternal data were analyzed. Results Among the 345 cases of abnormal USM,there were 152 cases with single USM,149 cases with other prenatal diagnosis indications,and 44 cases with multiple USM.The detection rates of pathogenic chromosomal abnormalities were 2.63% (4/152),10.74% (16/149) and 20.45% (9/44),respectively.The difference in detection rates between the three groups was statistically significant (χ²= 15.932,P<0.001).The detection rate of pathogenic chromosomal abnormalities with different USM ranged from 0.00% to 21.43%.The USM with the highest detection rate of pathogenic chromosomal abnormalities was nuchal fold (NF) thickening (21.43%),followed by nasal bone loss/dysplasia (12.68%).In the 345 cases,the detection rate of karyotyping chromosomal abnormalities was 7.27% (25/345),and the detection rate of CMA was 14.53% (50/345).No abnormality was detected by CMA in 4 fetuses with chromosomal abnormality by karyotyping.Among cases with normal karyotypes,29 copy number variation (CNV) were detected by CMA. Conclusion The fetus with NF thickening,nasal bone loss/dysplasia,multiple USM abnormalities or single USM abnormality combined with other prenatal indications have a higher detection rate of pathogenic chromosomal abnormality.Therefore,it is recommended to conduct interventional prenatal diagnosis.The results of karyotyping and CMA can be mutually verified and supplemented to provide a more accurate and effective genetic diagnosis for fetuses with abnormal USM.