Identification of high confidence genes involved in the manifestation of ventricular septal defect

Chaithra, S. and Nallur Basappa, R (2025) Identification of high confidence genes involved in the manifestation of ventricular septal defect. Egyptian Journal of Medical Human Genetics, 26 (1). ISSN 11108630

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Abstract

Background: Ventricular septal defect (VSD) is one of the common congenital heart malformations. Potential risk genes involved in the manifestation of VSD still need to be identified. Methods: The whole exome sequencing was performed on 24 congenital heart disease (CHD) subjects, 19 with VSD, two with VSD-associated atrial septal defects (ASD), and three with tetralogy of fallot (ToF). Besides, data mining using two CHD databases, a knowledgebase for nonsyndromic congenital heart disease-associated risk factors (CHD-RF-KB), and CHDbase and PubMed using medical subject headings were performed to prioritize the genes for further analysis in our study. The functional effects of variations of the selected genes were assessed using prediction tools to check the variant pathogenicity. The protein–protein network was established to identify the interactions among the proteins and their role in heart developmental pathways. Results: The whole exome sequencing analysis identified 628 genes with variants of minor allele frequency < 1%. In addition, the data mining yielded 50 genes, and of these, 34 genes were common in our 24 CHD subjects with new variations. Of the 34 genes, 11 genes, such as DLC1, MTRR, EVC, HOMEZ, EPRS, HOXB1, MTHFD1, MTHFR, NOS3, TRDN, and TBX18 recurrently occurred in more than 15 CHD subjects. The variant, c.524C > T in MTRR, recurrently occurred in nine CHD subjects, which resulted in the change of an amino acid from serine to leucine, suggesting a change in the functionality of the protein. Besides, four variations in GATA4 and one in TBX20 showed high pathogenicity scores. The protein–protein network showed high interactions among 26 transcription factors, and the TNNT2, MYL7, and ZFPM2 were the newly identified proteins in the network. Conclusions: The present study identified 37 potential risk genes through exome sequencing and interaction network analysis based on strong evidence from previously reported studies. From these genes, 176 variations were identified, of which 166 were newly reported from our samples, and 10 were previously reported, indicating that these are novel variants for the Indian population. Therefore, these genes and the variations can be a potential biomarker for creating the gene panel for CHD. © The Author(s) 2025.

Item Type:	Article
Uncontrolled Keywords:	Genes; Genomics; Network analysis; Variations; Ventricular septal defect; Whole exome sequencing
Subjects:	B Life Science > Genetics and Genomics
Divisions:	Department of > Genetics and Genomics
Depositing User:	Vasantha library uom
Date Deposited:	26 Nov 2025 10:15
Last Modified:	26 Nov 2025 10:15
URI:	http://eprints.uni-mysore.ac.in/id/eprint/18067

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