孤立型室间隔缺损胎儿的基因组拷贝数变异分析及文献回顾

Analysis of genome copy number variations in fetuses with isolated ventricular septal defect and a literature review

目的评估拷贝数变异(CNVs)检测对于孤立型室间隔缺损(VSD)胎儿遗传学病因的诊断价值。方法选取2017年12月至2020年12月郑州大学第一附属医院超声检查发现的69例孤立型VSD胎儿,同时检索万方、万方医学、中国知网等数据库,2016年1月1日至2021年1月1日以"室间隔缺损""拷贝数变异"以及"产前"为关键词,连同文献报道的839例胎儿,共计908例孤立型VSD胎儿作为研究对象。对69例胎儿进行低深度全基因组测序,并合并文献数据进行回顾性分析。结果在908例样本中,共检出33例致病性异常,总体检出率为3.63%。其中包括11例(1.21%)非整倍体以及22例(2.42%)致病性CNVs。后者涉及12种综合征,具体包括5例22q11.21缺失、2例4q末端缺失以及1例9q亚端粒缺失,均与心脏发育相关。22例致病性CNVs胎儿中,15例具有已知的妊娠结局,12例为自主终止妊娠,3例出生后室间隔自然闭合,但其中1例具有其他异常。结论孤立型VSD的胎儿具有较高的染色体异常检出率,因此建议对其进行CNV-seq检测。

Objective To assess the value of copy number variation sequencing(CNV-seq)for revealing the genetic etiology of fetuses with isolated ventricular septal defect(VSD).Methods From December 2017 to December 2020,69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University.Meanwhile,839 similar prenatal cases were selected from public databases including Wanfang data,Wanfang Medicine,and China National Knowledge Infrastructure(CNKI)by using keywords such as"Ventricular septal defect","Copy number variation",and"Prenatal".A total of 908 fetuses with isolated VSD were analyzed.CNV-seq was carried out for 69 fetuses.Results Among the 908 fetuses,33(3.63%)were found to harbor pathogenic CNVs,which included 11 chromosomal aneuploidies(1.21%)and 22 pathogenic CNVs(2.42%).The pathogenic CNVs have involved 12 genetic syndromes,with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome,2 cases of 4q terminal deletion syndrome,and 1 case of 9q subtelomere deletion syndrome.The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known,of which 12 were terminated,and 3 had spontaneous closure of the ventricular septum after birth,but 1 of them had other abnormalities.Conclusion Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities,for which CNV-seq should be recommended.