Detection of Copy Number Variants by Next-Generation Sequencing in Fetuses with Congenital Heart Disease

Abstract

Objective: To report the molecular findings of 89 fetuses with prenatal ultrasound diagnosis of congenital heart disease (CHD) and a normal karyotype through next-generation sequencing (NGS) in an attempt to improve our understanding of submicroscopic abnormalities present in malformed fetuses. Method: High-throughput NGS was carried out in fetal cord blood samples. All potential cytogenetic alterations detected on NGS platforms were matched against the known copy number variant (CNV) database. Results: A total of 204 CNVs were identified in the entire population of 89 fetuses with CHD. Eleven cases had no deletions or duplications, five cases (5.6%) had pathogenic CNVs, 13 cases had CNVs that were likely to be pathogenic, 42 cases had CNVs of uncertain significance, and 18 cases had benign and/or likely benign CNVs. All pathogenic CNVs were found only in fetuses with conotruncal heart defects. Conclusion: NGS can facilitate etiological diagnosis in a high proportion of fetuses with CHD and a normal karyotype and can be implemented as a diagnostic tool in the prenatal setting to complement karyotyping for evaluation of genomic defects in fetuses with CHD.