Background: Congenital heart disease (CHD) is one of the most common birth defects; however, the mechanisms underlying its development are poorly understood. Recently, heritable genetic factors, including copy number variations (CNVs) and single nucleotide polymorphisms (SNPs), have been implicated in its etiology. The aim of this study was to investigate the utility of a SNP array for the prenatal diagnosis of CHD and the improvement of prenatal genetic counseling and to compare this approach to traditional chromosome analysis.
Methods: One hundred and fortysix cases of CHD detected by prenatal echocardiography were analyzed. Of these, 110 were isolated CHD and 36 were of CHD with extracardiac defects. SNP analysis was performed using the Affymetrix CytoScan HD platform, which was followed by karyotype analysis. All annotated CNVs were validated by fluorescence in situ hybridization.
Results: Karyotype analysis identified chromosomal abnormalities in 19 of 146 cases. In addition to the 15 chromosomal abnormalities that were consistent with the results of karyotype analysis, the SNP array identified abnormal CNVs in an additional 15.2% (22/145) cases; of these, 15 were pathogenic CNVs, three were variations of uncertain clinical significance, and four were benign CNVs. The rates at which the SNP array detected pathogenic CNVs differed significantly between cases of isolated CHD and CHD with extracardiac defects (13.6% vs. 72.2%, P = .001). The results of the SNP array also affected the rate of pregnancy termination.
Conclusion: Combining SNP array with cytogenetic analyses is particularly effective for identifying chromosomal abnormalities in CNVs in fetuses with CHD, which also affects obstetrical outcomes.