Identification of intronic-splice site mutations in GATA4 gene in Indian patients with congenital heart disease

•15 novel intronic variants and 5 missense mutations were identified in CHD patients.•Two branch point mutations effects were discussed.•Effect of ISE and ISS binding motifs in pre-mRNA splicing was analyzed by in silico analysis.

Congenital Heart Disease (CHD) is the most common birth defect among congenital anomalies that arise before birth. GATA4 transcription factor plays an important role in foetal heart development. Mutational analysis of GATA4 gene in CHD patients revealed five known heterozygous mutations (p.T355S, p.S377G, p.V380M, p.P394T and p.D425N) identified in exons 5 and 6 regions and fifteen intronic variants in the non-coding regions (g.76885T > C/Y, g.76937G > S, g.78343G > R, g.83073T > Y, g.83271C > A/M, g.83318G > K, g.83415G > R, g.83502A > C/M, g.84991G > R, g.85294C > Y, g.85342C > T/Y, g.86268A > R, g.87409G > A/R, g.87725T > Y, g.87813A > T/W). In silico analysis of these intronic variants identified two potential branch point mutations (g.83271C > A/M, g.86268A > R) and predicted effects of these on intronic splice sites as enhancer and silencer motifs. This study attempts to correlate the pattern of intronic variants of GATA4 gene which might provide new insights to unravel the possible molecular etiology of CHD.