OBJECTIVE

Aggregating evidence highlights the strong genetic basis underpinning congenital heart disease (CHD). Here was chosen as a prime candidate gene causative of human CHD predominantly because BMP4 was amply expressed in the embryonic hearts and knockout of in mice led to embryonic demise mainly from multiple cardiovascular developmental malformations. The aim of this retrospective investigation was to discover a novel mutation underlying human CHD and explore its functional impact.

METHODS

A sequencing examination of was implemented in 212 index patients suffering from CHD and 236 unrelated non-CHD individuals as well as the family members available from the proband carrying a discovered mutation. The impacts of the discovered CHD-causing mutation on the expression of and induced by BMP4 were measured by employing a dual-luciferase analysis system.

RESULTS

A new heterozygous mutation, NM_001202.6:c.318T>G;p.(Tyr106*), was found in a female proband affected with familial CHD. Genetic research of the mutation carrier's relatives unveiled that the truncating mutation was in co-segregation with CHD in the pedigree. The nonsense mutation was absent from 236 unrelated non-CHD control persons. Quantitative biologic measurement revealed that Tyr106*-mutant BMP4 failed to induce the expression of and , two genes whose expression is lost in CHD.

CONCLUSION

The current findings indicate as a new gene predisposing to human CHD, allowing for improved prenatal genetic counseling along with personalized treatment of CHD patients.