https://orcid.org/0000-0001-7673-2628
Abstract
Background
Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis.
Methods
Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing.
Results
In family A, a compound heterozygous variation in PLD1 gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant ZIC3: c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants PLD1: c.1132dupA and ZIC3: c.861delG were novel.
Conclusion
The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.
Data Sharing Statement
The data that support the findings of this study are available in the Figshare repository at https://doi.org/10.6084/m9.figshare.22046615.
Ethics Statement
The probands’ parents were consented for sample collection and subsequent analysis, and written informed consent was obtained from the probands’ parents for publication and accompanying images.
Acknowledgments
The authors are grateful to the patients and the family members who participated in this study.
Disclosure
The authors have declared no conflicts of interest in this work.