High-risk genes involved in common septal defects of congenital heart disease

Gene. 2022 Oct 5:840:146745. doi: 10.1016/j.gene.2022.146745. Epub 2022 Jul 18.


The septation defect is one of the main categories of congenital heart disease (CHD). They can affect the septation of the atria leading to atrial septal defect (ASD), septation of ventricles leading to ventricular septal defect (VSD), and formation of the central part of the heart leading to atrioventricular septal defect (AVSD). Disruption of critical genetic factors involved in the proper development of the heart structure leads to CHD manifestation. Because of this, to identify the high-risk genes involved in common septal defects, a comprehensive search of the literature with the help of databases and the WebGestalt analysis tool was performed. The high-risk genes identified in the analysis were checked in 16 Indian whole-exome sequenced samples, including 13 VSD and three Tetralogy of Fallot for in silico validation. This data revealed three variations in GATA4, i.e., c.C1223A at exon 6: c.C602A and c.C1220A at exon 7; and one variation in MYH6, i.e., c.G3883C at exon 28 in two VSD cases. This study supports previously published studies that suggested GATA4 and MYH6 as the high-risk genes responsible for septal defects. Thus, this study contributes to a better understanding of the genes involved in heart development by identifying the high-risk genes and interacting proteins in the pathway.

Keywords: Atrial septal defect; Atrioventricular septal defect; Congenital heart disease; Septal defect genes; Ventricular septal defect.

Publication types

  • Systematic Review

MeSH terms

  • Exome
  • Heart Defects, Congenital* / genetics
  • Heart Septal Defects* / genetics
  • Heart Septal Defects, Atrial* / genetics
  • Heart Septal Defects, Ventricular* / genetics
  • Heart Septal Defects, Ventricular* / metabolism
  • Humans