Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease.

BACKGROUND: Congenital heart disease is the most common birth defect in newborns in southern China. The germline mutations in GATA4, NKX2.5, and TFAP2B genes have been identified to be responsible for congenital heart disease. The frequency of GATA4, NKX2.5, and TFAP2B mutations in subjects with congenital heart disease in southern China and the correlation between their genotype and congenital heart disease phenotype are not known.

METHODS: We screened germline mutations in the coding exons and the flanking intron sequences of the GATA4, NKX2.5, and TFAP2B genes in 224 congenital heart disease patients located in southern China by denaturing high-performance liquid chromatography and DNA sequencing.

RESULTS: Fifteen heterozygous mutations in the GATA4 gene were identified in 30 congenital heart disease patients, including a novel heterozygous missense mutation (c.788 C>G) of GATA4 in one patient with ventricular septal defect. A novel TFAP2B mutation (c.31 A>G) in a patient with endocardial cushion defect and an unreported novel TFAP2B variant (c.1006 G>A) in six patients suffering from tetralogy of Fallot (one patient), persistent truncus arteriosus (two patients) and patent ductus arteriosus (three patients) was found. There were no reported NKX2.5 mutations except for several single nucleotide polymorphisms in the patients.

CONCLUSION: These results suggest that genomic GATA4 and TFAP2B missense mutations may be associated with nonfamilial congenital heart disease with diverse clinical phenotypes in patients with congenital heart disease from southern China. They also revealed that the variation of the NKX2.5 gene may not be a risk factor for sporadic patients with congenital heart disease in this population.