Related Experiment Video
Updated: Aug 6, 2025
Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound 30/45MHZ System
Published on: May 5, 2018
Detection of Novel Pathogenic Variants in Two Families with Recurrent Fetal Congenital Heart Defects
Rongqin Cai1, Ya Tan1, Mingming Wang2
1Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, 102206, People's Republic of China.
Insights
This study identified novel genetic variants in congenital heart disease (CHD) using whole-exome sequencing. These findings aid in understanding CHD causes and offer genetic counseling for families.
Area of Science:
- Genetics
- Developmental Biology
- Medical Genetics
Background:
- Congenital heart disease (CHD) is a common birth defect with complex genetic causes.
- Over 400 genes are implicated in heart development, highlighting genetic heterogeneity.
- Genetic analysis is vital for CHD management and understanding its etiology.
Purpose of the Study:
- To identify genetic variants in fetuses with congenital heart disease.
- To demonstrate the clinical utility of whole-exome sequencing (WES) in prenatal diagnosis.
- To provide genetic insights for affected families regarding recurrence risks and reproductive options.
Main Methods:
- Whole-exome sequencing (WES) was employed on DNA from fetuses and parents in two independent CHD cases.
- Aneuploidy and large copy number variations (CNVs) were excluded.
- WES findings were validated using Sanger sequencing.
Main Results:
- Novel compound heterozygous variants (c.1132dupA and c.1171C>T) in the PLD1 gene were identified in a fetus from family A.
- A novel hemizygous variant (c.861delG) in the ZIC3 gene was found in a fetus from family B.
- Both identified variants in PLD1 and ZIC3 were confirmed as novel.
Conclusions:
- The study identified novel variants contributing to the congenital heart disease mutation spectrum.
- Findings offer crucial evidence for recurrence risks and reproductive counseling for affected families.
- Whole-exome sequencing shows significant potential for clinical application in prenatal diagnosis of CHD.
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.
