ObjectiveTo investigate the abnormal sonographic phenotypes and genetic examination in fetuses with ventricular septal defect（VSD）

and to provide information of prenatal counseling and prognosis assessment.MethodsSeventyseven fetuses with VSD diagnosed by echocardiography were selected

and their data of karyotype analysis

chromosome microarray analysis（CMA）

whole exome sequencing（WES）and copy number variation sequencing（CNV-seq）were complete

and follow-ups were performed until termination of pregnancy. The analysis of the heart

heart ultrasonic structure abnormal phenotype and genetic examination were conducted.ResultsAmong the 77 VSD fetuses

41 cases（53.2%）were isolated VSD which was the most

16 cases（20.8%）were VSD combined with cardiac and extracardiac malformations

14 cases（18.2%）were VSD combined with cardiac malformation

and 6 cases（7.8%）were VSD combined with extracardiac malformation. Ultrasound phenotypic abnormalities:22 cases（28.6%） were VSD combined with extracardiac malformations

in which ultrasonic microstructural abnormalities was the most common

and 30 cases（39.0%）were VSD combined with cardiac abnormalities

in which were all conus arteriosus malformations. There were 16 cases with genetic abnormalities

and the detection rate was20.8%. Among them

the highest rate was found in fetuses with VSD combined with cardiac and extracardiac malformations

which was 43.8%（7/16）

followed by 35.7%（5/14）with VSD combined with cardiac malformations

VSD combined withextracardiac malformation account for 33.3%（2/6）and isolated VSD account for 4.9%（2/41）.12 abnormal cases were detected in normal karyotype VSD fetuses

including 8 cases of pathogenic CNVs（6 cases of microdeletions and 2 cases of microduplication）

and 4 cases of monogenic diseases. The molecular diagnostic rates were increased by 15.1% and 7.5%

respectively.ConclusionIntracardiac and extracardiac abnormalities should be carefully examined when VSD is detected in fetuses and perform genetic examination at the same time. Applying the methods including karyotype

CMA

WES

CNV-seq comprehensively and rationally can improve the detection rate of genetic abnormalities in VSD fetuses

and provide more information for prenatal evaluation and prognostic counseling.