染色体微阵列分析在胎儿超声异常与染色体异常中的应用

Application of chromosomal microarray analysis in fetal ultrasonic anomalies and chromosome abnormalities

目的探讨染色体微阵列分析(CMA)在产前超声异常与胎儿染色体异常关系中的临床应用价值。方法选取2017年7月-2018年12月在福建医科大学附属福州市第一医院就诊的328例产前超声异常孕妇为研究对象,分析其CMA检测结果,分层统计不同超声异常种类中染色体异常的检出率,分析染色体异常结果的构成和相关特性。结果在328例产前诊断病例中,超声结构异常共111例,检出染色体异常24例,检出率为21.6%,其中多系统结构异常13例,检出染色体异常7例,检出率为53.8%;孤立系统异常检出率为10.0%~30.8%。软指标异常共207例,检出染色体异常32例,检出率为15.5%,其中多项软指标异常109例,检出染色体异常16例,检出率为14.7%。单独胎儿生长受限3例,检出染色体异常1例,检出率为33.3%。共发现染色体异常57例,检出率为17.4%,其中发现基因组拷贝数变异(CNVs)明确致病性共23例,占染色体异常的40.4%,包含染色体数目异常14例及致病性染色体片段异常9例;良性CNVs共8例,占染色体异常的14.0%;临床意义不明的CNVs(VOUS)26例,占总病例数的7.9%,进一步分析判读CNV为可能良性6例,可能致病4例,临床意义不明16例。结论超声异常是筛查胎儿染色体异常的关键指征,超声结构异常的染色体异常检出率高于超声非结构异常的检出率。当超声结构异常出现两项及以上时,染色体异常发生率会明显增高。但随着检出率的提高,VOUS病例数同时也随之增多,增加了遗传学咨询难度。因此在产前诊断中需合理推荐CMA检测,避免漏诊、误诊或过度诊断。

Objective To explore the clinical application value of chromosomal microarray analysis(CMA)in fetal ultrasonic anomalies and chromosome abnormalities.Methods From July 2017 to December 2018,328 pregnant women with prenatal ultrasonic anomalies were selected from the First Hospital of Fuzhou as study object,CMA results were analyzed,the detection rates of chromosome abnormalities in pregnant women with different ultrasonic anomalies were analyzed statistically,the composition and related characteristics of chromosome abnormalities were analyzed.Results Among 328 cases,111 cases were found with ultrasonic anomalies,24 cases were found with chromosome abnormalities,the detection rate was 21.6%.Among 13 cases with multiple system structural abnormalities,7 cases were found with chromosome abnormalities,the detection rate was 53.8%;the detection rate of single system structural abnormalities ranged from 10.0%to 30.8%.Among 207 cases with soft index anomalies,32 cases were found with chromosome abnormalities,the detection rate was 15.5%;among 109 cases with multiple soft index anomalies,16 cases were found with chromosome abnormalities,the detection rate was 14.7%.Among 3 cases with fetal growth restriction,one case was found with chromosome abnormalities,the detection rate was 33.3%.A total of57 cases were found with chromosome abnormalities,the detection rate was 17.4%,23 cases were found with genome copy number variations(CNVs)of identify pathogenicity,accounting for 40.4%,including14 cases with chromosomal numerical abnormalities and 9 cases with pathogenic chromosomal fragment abnormalities,8 cases were found with malignant CNVs,accounting for 14.0%;26 cases were found with CNVs of uncertain significance(VOUS),accounting for 7.9%,further analysis showed that there were probably benign findings in 6 cases,probably pathogenic findings in 4 cases,and uncertain clinical significance in 16 cases among the cases with CNVs.Conclusion Ultrasonic anomalies are key indications of screening fetal chromosome abnormalities,the detection rate of chromosome abnormalities in cases with structural abnormalities is higher than that in cases without structural abnormalities.The incidence rate of chromosome abnormalities increases significantly in cases with two or more than two types of structural abnormalities.With the increase of detection rate,the number of VOUS cases increases,which enhances the difficulty of genetic counseling.CMA should be used reasonably in prenatal diagnosis to avoid missed diagnosis,misdiagnosis,or over-diagnosis.