Exploration of copy number variations and candidate genes in fetal congenital heart disease using chromosomal...

This study aimed to investigate copy number variations (CNVs) and potential candidate genes associated with fetal congenital heart disease (CHD) and to compare the prevalence of CNVs among different CHD subtypes.

A retrospective analysis was performed on 391 fetuses diagnosed with CHD between 2019 and 2023. 391 fetuses with case were divided into three groups: isolated CHD (Group 1), complex CHD (Group 2), and CHD with extracardiac anomalies (Group 3). Amniocentesis was performed for all pregnant women, with both karyotyping and CMA conducted. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted for isolated and complex CHD cases.

CMA and karyotype detected total abnormalities in 22 % of all CHD fetuses, including a chromosomal aneuploidy rate of 7.2 %, a pathogenic CNV (pCNV) rate of 6.1 %. The overall detection rates for Groups 1, 2, and 3 were 11.6 %, 12.5 %, and 50 %, respectively. Group 3 exhibited significantly higher rates of chromosomal aneuploidy (23.7 %) and pCNV (17.8 %) compared to Groups 1 and 2 (p < 0.001). No significant differences in maternal age were observed among the three CHD groups. KEGG pathway analysis identified the top three enriched pathways for complex CHD were nucleocytoplasmic transport, cell adhesion molecules, and the mRNA surveillance pathway.

The rates of chromosomal aneuploidy and CNV abnormalities in CHD cases with extracardiac anomalies were significantly higher than in the other two groups. Maternal age was not associated with the chromosomal abnormalities observed in CHD cases. KEGG pathway analysis indicated more intricate molecular pathways in complex CHD.