Identification of two novel GATA6 mutations in patients with nonsyndromic conotruncal heart defects

GATA binding protein 6 (GATA6) encodes a zinc‑finger transcription factor that is essential for normal heart development. Mutations in this gene lead to conotruncal heart defects associated with cyanotic congenital heart disease; however, it remains unclear whether the mutations in GATA6 are also responsible for the development of the nonsyndromic conotruncal heart defects. The coding region exons and flanking intron sequences of GATA6 were screened in 157 patients with nonsyndromic conotruncal heart defects and 300 control subjects. Three heterozygous missense mutations, c.151G>A (E51K), c.551G>A (S184N) and c.733G>C (G245R), were identified in patients with tetralogy of Fallot or persistent truncus arteriosus. The two novel mutations (E51K and G245R) identified in the current study are located in evolutionarily conserved residues of the GATA6 protein. It was demonstrated that these two mutations lead to a significant reduction in the transactivation capacity of downstream genes. The current study presents two novel GATA6 mutations in patients with nonsyndromic conotruncal heart defects and provides novel insights into the pathogenesis of this disease.