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Updated: Jan 13, 2026
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Identifying Pathogenic Variants in Vietnamese Children with Functional Single Ventricle Based on Whole-Exome
Le Trong Tu1,2, Nguyen Thi Kim Lien3, Nguyen Van Tung3,4
1Department of Pediatrics, Hanoi Medical University, Hanoi 100000, Vietnam.
Insights
This study identifies genetic variants in functional single ventricle (FSV) patients, revealing potential causes for this complex congenital heart disease. Findings guide future treatment and prevention strategies for FSV.
Area of Science:
- Genetics
- Cardiology
- Developmental Biology
Background:
- Functional single ventricle (FSV) is a complex congenital heart disease (CHD) with multifactorial etiology.
- Identifying specific pathogenic factors for FSV is challenging, hindering effective interventions and prevention.
Purpose of the Study:
- To identify genetic variants associated with functional single ventricle (FSV) using whole-exome sequencing.
- To understand the genetic underpinnings of FSV to inform treatment and prevention.
Main Methods:
- Whole-exome sequencing (WES) was conducted on 29 patients with functional single ventricle (FSV).
- Analysis focused on identifying heterozygous variants in CHD-associated genes.
Main Results:
- Ninety-five heterozygous variants across 48 CHD-associated genes were identified in FSV patients.
- Key genes with variants include AXIN1, BMP2, GATA4, MYH6, NOTCH1, and TBX genes, among others.
- Variants in COL6A1, CREBBP, MYBPC3, and MYH7 were associated with FSV phenotypes like septal defects and great artery transposition.
Conclusions:
- This is the first study to report genetic variants linked to functional single ventricle (FSV).
- The identified variants offer insights into the genetic causes of FSV.
- Findings can guide the development of targeted treatment and prevention strategies for FSV.
Abstract:
Background: Functional single ventricle (FSV) comprises a heterogeneous group of congenital heart diseases (CHDs) with severe and complex abnormalities. The multifactorial etiology of the disease poses challenges in identifying specific pathogenic factors and planning effective interventions and preventive treatments for patients. Methods: Whole-exome sequencing (WES) was performed to identify variants in relevant genes in 29 FSV patients from different families. Results: In total, 95 heterozygous variants across 48 CHD-associated genes were identified, including 85 missense, four small indel, one splicing, one stop gain, and four synonymous variants. Among them, 22 were novels, 11 conflicting, and four pathogenic variants. Each patient carried from two to six variants in different genes, including at least one variant in genes associated with serious heart defects such as AXIN1, BMP2, COL6A2, GATA4, GATA5, GDF1, MESP1, MYH6, NFATC1, NKX2-6, NOTCH1, PCSK9, TBX1, TBX18, and TBX20. In addition, the variants in the COL6A1, CREBBP, DOCK6, EOGT, EP300, LRP2, MYBPC3, MYH7, SEMA3C, and ZFPM2 genes are associated with characteristic phenotypes of FSV, such as atrial septal defect, ventricular septal defect, small left heart syndrome, transposition of the great arteries, and double outlet right ventricle occurring at high frequency in patients. The prediction results suggest that these are potentially pathogenic variants in patients and may explain the phenotype in patients. Conclusions: This is the first study to identify variants associated with functional single ventricle, a complex form of congenital heart disease. Our results contribute to a general understanding of the causes of the disease, thereby guiding treatment and prevention approaches for patients.
