77例室间隔缺损胎儿产前超声及遗传学检查结果分析

目的 探讨室间隔缺损(VSD)胎儿常见超声异常表型及遗传学结果,为产前咨询及预后评估提供资料。方法 对2016年11月至2018年12月我院超声心动图诊断VSD胎儿进行染色体核型分析、染色体微阵列分析(CMA)、低深度全基因组测序方法(CNV-seq)、全外显子测序(WES)等遗传学检测。以遗传学检测资料完整并随访至妊娠终止的77例VSD胎儿作为研究对象,回顾性分析其心脏及心外超声结构异常表型、遗传学检查结果。结果 1.77例VSD胎儿中：孤立性VSD胎儿41例(53.2%),VSD同时合并心脏及心外畸形16例(20.8%)、VSD只合并心脏畸形14例(18.2%)、VSD只合并心外畸形6例(7.8%)。2.超声表型异常：合并心外畸形22例(28.6%),以超声微小结构异常最常见；合并心脏异常30例(39%),均为圆锥动脉干畸形。3.遗传学异常共16例,检出率20.8%(16/77)：VSD同时合并心脏及心外畸形胎儿遗传学异常率最高,为43.8%(7/16), 其次为VSD只合并心脏畸形胎儿35.7%(5/14)、VSD只合并心外畸形胎儿33.3%(2/6)、孤立性VSD胎儿4.9%(2/41)。在核型正常VSD胎儿中额外检出12例异常：致病性CNVs 8例(6例微缺失、2例微重复)、4例单基因病,分子诊断率分别提高了15.1%、7.5%。结论 产前超声发现胎儿存在VSD时,应仔细扫查是否合并心脏及心外异常,并进行遗传学检测；综合合理应用包括核型,CMA及高通量测序(WES, CNV-seq)等方法能提高VSD胎儿遗传学异常检出率,对VSD胎儿的产前评估和预后咨询能提供更多信息。

Analysis of prenatal ultrasound and genetic examination of 77 fetuses with ventricular septal defect

Objective To investigate the abnormal sonographic phenotypes and genetic testing of Ventricular septal defect (VSD) in fetus, and to provide information for prenatal counseling and prognosis assessment. Methods From November 2016 to December 2018, 234 fetus with VSD were diagnosed by echocardiography. Amniocentesis or cord blood puncture was voluntarily selected when discover ultrasound abnormalities for karyotype analysis, chromosome microarray analysis (CMA),and whole exome sequencing (WES). WES/Whole genome sequencing (WGS) was performed by obtain fetal umbilical cord tissue and deltoid. Results 1.Of the 77 VSD fetuses, the proportion of isolated VSD fetuses was the highest, 53.2%(41/77), followed by VSD combined with intracardiac and extracardiac malformations 20.8% (16/77) , VSD combined with intracardiac malformation 18.2% (14/77), VSD combined with extracardiac malformation 7.8% (6/77). 2. Ultrasound phenotypic abnormalities: 22 cases (28.6%) with extracardiac abnormalities, the most was minorabnormalities of ultrasound; 30 cases (39%) with intracardiac abnormalities, all of which were conotruncal defect.3. There were 16 cases of genetic abnormalities, and the detection rate was 20.8%: the proportion of VSD combined with intracardiac and extracardiac malformations was the highest, 43.8% (7/16), followed by VSD with intracardiac malformation 35.7%(5/14), VSD with extracardiac malformation 33.3%(2/6), isolated VSD 4.9%(2/41). Using CMA and WES techniques, 12 additional abnormalities were detected in karyotype normal VSD fetuses: 8 cases of pathogenic CNVs (6 cases of microdeletions, 2 cases of microduplication), 4 cases of monogenic diseases, and the molecular diagnostic rates were improved respectively 15.1%, 7.5%.Conclusions Intracardiac and extracardiac abnormalities should be carefully examined when VSD was detected in fetus; CMA and WES can improve the detection rate of VSD fetal genetic abnormalities, and provide more information for prenatal evaluation and prognostic counseling.