Novel mutations of the SRF gene in Chinese sporadic conotruncal heart defect patients

Background Conotruncal heart defects (CTDs) are a group of congenital heart malformations that cause anomalies of cardiac outflow tracts. In the past few decades, many genes related to CTDs have been reported. Serum response factor (SRF) is a ubiquitous nuclear protein that acts as transcription factor, and SRF was found to be a critical factor in heart development and to be strongly expressed in the myocardium of the developing mouse and chicken hearts. The targeted inactivation of SRF during heart development leads to embryonic lethality and myocardial defects in mice.Results To illustrate the relationship between SRF and human heart defects, we screened SRF mutations in 527 CTD patients. Two novel mutations (p.G274D and p.G294C) of SRF were identified. Western blotting and real-time PCR showed that there were no obvious differences between the protein expression and mRNA transcription of mutants and wild-type SRF. A dual luciferase reporter assay showed that both SRF mutants (G274D and G294C) impaired SRF transcriptional activity at the SRF promoter and atrial natriuretic factor (ANF) promoter (p<0.05), additionally, the mutants displayed reduced synergism with GATA4.Conclusion These results suggest that SRF-p.G274D and SRF-p.G294C may have potential pathogenic effects.