199例妊娠中晚期胎儿室间隔缺损的遗传学因素研究

  目的  探讨单核苷酸多态性微阵列芯片技术(single nucleotide polymorphism array，SNP array)检测胎儿室间隔缺损的遗传学病因的应用价值。  方法  回顾性分析2015年1月—2020年12月在广西壮族自治区妇幼保健院就诊的199例妊娠孕中期或孕晚期胎儿室间隔缺损的孕妇资料, 行羊膜腔穿刺抽取羊水标本或脐静脉穿刺抽取脐带血标本, 分析其染色体核型结果与基因芯片结果，结合查询拷贝数变异(copy number variations，CNVs)数据库、DGV以及PubMed等数据库对检出的CNV的致病性进行分析。  结果  199例胎儿羊水或脐带血染色体核型异常27例，检出率为13.57%，其中22例染色体非整倍体异常，5例染色体结构异常。SNP array检出41例异常，检出率为20.60%(41/199)，SNP array异常检出率稍高于染色体核型异常检出率；芯片异常中有32例致病性，其中27例与核型分析结果一致，5例核型未见异常而芯片检出染色体微缺失综合征，另外9例为临床意义不明的染色体微缺失/微重复。  结论  孕中晚期产前诊断胎儿室间隔缺损以染色体非整倍体为主，SNP array技术可检测出亚显微致病性CNV，为胎儿室间隔缺损的遗传咨询和预后评估提供依据。 

Genetic factors of ventricular septal defect in 199 cases in the second or third trimester of pregnancy

  Objective  This study aims to explore the application value of single-nucleotide polymorphism array (SNP array) in the genetic aetiology of foetal ventricular septal defect.  Methods  A retrospective analysis was performed on 199 cases of foetal ventricular septal defect during the second or third trimester of pregnancy in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to December 2020. Amniocentesis was performed to extract amniotic fluid samples, or umbilical cord venipuncture was performed to extract umbilical cord blood samples. Chromosome karyotype and gene chip were analysed. The pathogenicity of detected CNV was analysed by querying CNV, DGV and PubMed databases.  Results  Twenty-seven cases of foetal amniotic fluid or cord blood chromosomal karyotype abnormalities were detected, with rate of 13.57%. Moreover, 22 cases of chromosome aneuploidy abnormality and 5 cases of chromosome structure abnormality were found. The SNP array detected 41 abnormalities, with the detection rate of 20.60% (41/199). The detection rate of SNP array abnormalities was slightly higher than that of chromosomal karyotype abnormalities; among the cases of microarray abnormalities, 32 cases were pathogenic; of which, 27 cases were consistent with the results of the karyotype analysis, 5 cases showed no abnormal karyotype but the chip detected chromosome microdeletion syndrome and the 9 other cases had chromosome microdeletion/microduplication of unknown clinical significance.  Conclusion  Chromosomal aneuploidy is the main diagnosis of foetal ventricular septal defect in the second or third trimester of pregnancy. SNP array detection technology can detect sub-microscopic pathogenic CNV and provide basis for genetic counselling and prognosis evaluation of foetal ventricular septal defect.