Association of GATA4 Gene Variants with Congenital Heart Disease: A Case–control Study

BACKGROUND: Congenital heart disease (CHD) is one of the most common birth defects in infants and significantly impacts life expectancy. Nonsyndromic CHDs are more severe than syndromic clinical phenotypes, with life expectancy often limited to days or weeks. It is imperative to evaluate genes associated with CHD or developmental defects at the population level to ascertain their severity and inform appropriate therapeutic interventions. This study aimed to evaluate GATA4 gene variants in sporadic congenital heart defects in children in the rural Vidarbha region. MATERIALS AND METHODS: We collected blood samples from 40 clinically proven nonsyndromic CHD for genotyping the GATA4 gene. All the children had normal cytogenetic profiles. We performed specific genotyping of exon 4 of the GATA4 gene using Sanger sequencing. In silico analyses, including Mutation Taster, PolyPhen2, Missense3D, HOPE, and SwissModel, were performed to evaluate the disease-causing effects of detected variants in exon 4 of GATA4 gene. RESULTS: Our analysis identified three novel missense exonic nucleotide variants, E287K (c. 859G > A, p. Glu287Lys), G296A (c. 887G > C, p. Gly296Ala), and K300R (c. 899A > G, p. Lys300Arg), which were potentially deleterious according to in silico analysis. The present analysis indicates that the variants identified in this study are likely to be associated with CHD in children. CONCLUSION: Notably, we report for the first time these three novel variants in exon 4, which may represent potential risk factors for CHD development.