探讨单核苷酸多态性微阵列芯片(SNP-array)技术在胎儿侧脑室增宽产前诊断中的应用。

选择2016年1月至2018年10月，于广西壮族自治区妇幼保健院进行定期产前检查时，超声筛查提示胎儿侧脑室增宽的433例中、晚孕期孕妇为研究对象。孕妇年龄为19～45岁，孕龄为16^＋6～37^＋6孕周，其中，中孕期为135例(31.2%)，晚孕期为298例(68.8%)。回顾性分析433例孕妇的胎儿染色体核型分析结果及SNP-array检测结果。本研究经广西壮族自治区妇幼保健院伦理委员会批准[医研伦快审(2019)第(3-21)号]，并与受试者签署临床研究知情同意书。

①135例行羊膜腔穿刺术产前诊断的中孕期孕妇中，检出胎儿染色体核型异常为22例，异常检出率为16.3%(22/135)。298例行脐静脉穿刺术产前诊断的晚孕期孕妇中，检出胎儿染色体核型异常为17例，异常检出率为5.7%(17/298)。②135例中孕期孕妇羊水样本中，SNP-array检出胎儿染色体异常为28例，异常检出率为20.7%(28/135)。298例晚孕期孕妇脐血样本中，SNP-array检出胎儿染色体异常为37例，异常检出率为12.4%(37/298)。SNP-array检出的65例胎儿染色体异常孕妇中，39例(60.0%)为胎儿染色体核型分析异常者，而26例(40.0%)为胎儿染色体核型分析结果正常者。这26例胎儿染色体核型分析结果正常、SNP-array检测结果异常孕妇中，其胎儿发生致病性拷贝数变异(CNVs)者为11例(7例染色体微缺失、1例染色体微重复、3例染色体微缺失合并微重复)；胎儿发生疑似致病性CNVs者为1例(染色体微缺失)；胎儿发生临床意义不明CNVs者为14例(5例染色体微缺失、4例染色体微重复、5例为1条或多条染色体间杂合性缺失)。

对产前超声筛查提示胎儿侧脑室增宽的中、晚孕期孕妇，进行SNP-array检测，有助于发现胎儿染色体核型分析无法检出的胎儿染色体亚显微结构异常。

To explore the application of single nucleotide polymorphism array (SNP-array) technology in prenatal diagnosis of fetal lateral ventriculomegaly.

From January 2016 to October 2018, 433 pregnant women with fetal lateral ventriculomegaly in the second and third trimester were selected as research subjects. The age ranged from 19 to 45 years old, and gestational age ranged from 16^{+ 6} to 37^{+ 6} weeks. Among them, 135 cases (31.2%) were in the second trimester and 298 cases (68.8%) in the third trimester. The fetal karyotype analysis results and SNP-array detection results of 433 pregnant women were analyzed retrospectively. This study was approved by the ethics committee of Maternal & Child Health Hospital of Guangxi Zhuang Autonomous Region [No. 2019 (3-21)]. Informed consent was obtained from each participate.

①Among the 135 pregnant women in the second trimester who underwent amniocentesis for prenatal diagnosis, 22 cases of fetal chromosomal karyotypic abnormalities were detected, with an abnormality detection rate of 16.3% (22/135). And 17 cases of fetal chromosomal karyotypic abnormalities were detected in 298 pregnant women in the third trimester undergoing routine umbilical venipuncture, with an abnormality detection rate of 5.7% (17/298). ② Among 135 amniotic fluid samples of pregnant women in the second trimester, 28 cases of fetal chromosomal abnormalities were detected by SNP-array, with an abnormality detection rate of 20.7% (28/135). Among the 298 cord blood samples of pregnant women in the third trimester, 37 cases of fetal chromosomal abnormalities were detected by SNP-array, with an abnormality detection rate of 12.4% (37/298). Among the 65 cases of abnormal results of SNP-array detection, 39 cases (60.0%) were abnormal with fetal karyotype analysis, and 26 cases (40.0%) were with normal fetal karyotype analysis results. Among the 26 cases with normal fetal karyotype analysis results while with abnormal SNP-array detection results, fetuses of 11 cases were pathogenic copy number variations (CNVs) (7 cases with chromosomal microdeletion, 1 case with chromosomal microduplication, and 3 cases with chromosomal microdeletion combined with microduplication); 1 case was suspected pathogenic CNVs (chromosomal microdeletion); 14 cases with unknown clinical significance of CNVs (5 cases with chromosome microdeletion, 4 cases with chromosome microdeletion, 5 cases with loss of heterozygosity between one or more chromosomes).

Among pregnant women with fetal lateral ventriculomegaly in the second and third trimester, SNP-array detection is helpful to find fetal abnormal chromosome submicroscopic structure which cannot be detected by fetal karyotype analysis.