Shiva Abbasi
1 
, Neda Mohsen-Pour
2, Niloofar Naderi
1, Shahin Rahimi
3, Majid Maleki
1, Samira Kalayinia
1* 1 Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
3 Department of Cardiology, Rajaie Cardiovascular Medical and Research Centre, Iran University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Congenital heart disease (CHD) is the most common congenital abnormality and the main cause of infant mortality worldwide. Some of the mutations that occur in the GATA4 gene region may result in different types of CHD. Here, we report our in silico analysis of gene variants to determine the effects of the GATA4 gene on the development of CHD.
Methods: Online 1000 Genomes Project, ExAC, gnomAD, GO-ESP, TOPMed, Iranome, GME, ClinVar, and HGMD databases were drawn upon to collect information on all the reported GATA4 variations.The functional importance of the genetic variants was assessed by using SIFT, MutationTaster, CADD,PolyPhen-2, PROVEAN, and GERP prediction tools. Thereafter, network analysis of the GATA4protein via STRING, normal/mutant protein structure prediction via HOPE and I-TASSER, and phylogenetic assessment of the GATA4 sequence alignment via ClustalW were performed.
Results: The most frequent variant was c.874T>C (45.58%), which was reported in Germany.Ventricular septal defect was the most frequent type of CHD. Out of all the reported variants of GATA4,38 variants were pathogenic. A high level of pathogenicity was shown for p.Gly221Arg (CADD score=31), which was further analyzed.
Conclusion: The GATA4 gene plays a significant role in CHD; we, therefore, suggest that it be accorded priority in CHD genetic screening.