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Whole-Exome Sequencing Identifies Novel GATA5/6 Variants in Right-Sided Congenital Heart Defects
Gloria K E Zodanu1,2, John H Hwang1,2, Jordan Mudery1,2
1Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
International Journal of Molecular Sciences
|March 13, 2025
Summary
New GATA5 and GATA6 gene variants are linked to congenital heart defects (CHDs). This study identifies novel genetic causes for right-sided CHDs, improving understanding of cardiovascular development and disease.
Area of Science:
- Genetics
- Developmental Biology
- Cardiology
Background:
- Congenital heart defects (CHDs) affect 1% of live births due to embryonic cardiovascular system maldevelopment.
- Transcription factors GATA5 and GATA6 are crucial for embryonic development; their inactivation can lead to CHDs.
Purpose of the Study:
- To investigate the genetic basis of right-sided CHDs in two families.
- To identify novel variants in GATA5 and GATA6 genes associated with congenital heart abnormalities.
Main Methods:
- Genotypic-phenotypic analysis using whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES).
- Echocardiography for CHD diagnosis and characterization.
- Segregation analysis to confirm variant inheritance patterns.
Main Results:
- A novel heterozygous GATA5 variant (p.Arg237Pro) was identified in a proband with pulmonary valve stenosis, inherited from the mother.
- A novel heterozygous GATA6 variant (p.Pro586Leu) was identified in a proband with complex right-sided CHD, inherited from the father.
- Both variants were absent in unaffected family members, supporting their pathogenic role.
Conclusions:
- Novel GATA5 and GATA6 variants are associated with a spectrum of right-sided congenital heart defects.
- These findings highlight the critical role of GATA5 and GATA6 in human cardiovascular development.
- Genotypic-phenotypic correlation provides insights into the etiology of CHDs.
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