Abstract: Objective    To study the clinical value of copy number variation（CNVs） in the etiological diagnosis of fetal congenital heart disease（CHD） and to supplement the potential causes of fetal CHD. Methods    A retrospective analysis was used in this study. A total of 3386 patients who underwent amniotic fluid puncture examination in Sichuan Maternal and Child Health Care Hospital from January 2020 to August 2022 were collected and divided into control group（2689 cases） and experimental group（697 cases）. The experimental group was further divided into 3 subgroups，namely， simple CHD，complex CHD and CHDwith extracardiac malformations. The difference in detection rate of CNVs pathogenicity was analyzed. Results    In the experimental group，a total of 53 cases of CNVs were detected，and 34 cases of pathogenic CNVs were detected，9 cases were CNVs of unknown clinical significance（VOUS），and 8 cases were potentially pathogenic，among which NF1，HNF1B and MAP3K20 might be related to the occurrence of fetal CHD.Conclusion    The detection rate of CNVs and chromosome karyotype abnormality of CHD in fetuses is significantly higher than that in normal fetuses. Chromosome microarray analysis can be used as a supplement to traditional chromosome karyotype analysis. Some CNVs（VOUS） phenotypes of unknown clinical significance remain to be further verified.

Key words: fetal congenital heart disease, copy number variation, genetic factors, chromosome microarray analysis

摘要： 目的    研究拷贝数变异（CNVs）在胎儿先天性心脏病（CHD）病因诊断的临床价值，对胎儿CHD的潜在病因进行补充。方法    采用回顾性分析法，收集2020年1月—2022年8月于四川省妇幼保健院行羊水穿刺检查者共3386人，分为对照组（2689例）及试验组（697例），其中试验组为3个亚组，即单纯型CHD，复杂型CHD，合并有心外畸形的CHD，分别分析其CNVs致病性检出率的差异性。结果    试验组病例中检出CNVs共53例，检出致病性CNVs共34例，9例为临床意义未明的CNVs（VOUS），有8例具有潜在致病性，其中NF1、HNF1B、MAP3K20可能与胎儿CHD的发生相关。结论    胎儿CNVs及染色体核型异常检出率明显高于正常胎儿。染色体芯片分析可作为传统染色体核型分析的补充。一些临床意义未知的VOUS表型仍有待进一步验证。

关键词: 胎儿先天性心脏病, 拷贝数变异, 遗传因素, 染色体微阵列分析