Recent studies have reported germline mutations in GATA4 gene in some types of congenital heart disease (CHD). However, the prevalence of GATA4 mutations in CHD and the correlation between the GATA4 genotype and CHD phenotype have not been extensively studied. We screened germline mutations in the coding exons and the flanking intron sequences of the GATA4 gene in 486 CHD patients by denaturing high-performance liquid chromatography (DHPLC), and confirmed the mutations by sequencing. Nine distinct mutations including one small deletion mutation (46deIS), two small insertion mutations (118-119insA and 125-126insAA), and six non-synonymous mutations (A6V, P163S, E359K, P407Q, S429T and A442V) were identified in 12 of the 486 patients (nine with ventricular septal defect, two with Tetralogy of Fallot, and one with endocardial cushion defect). Of them, two patients carrying E359K mutation were from two generations in one family with ventricular septal defect (VSD). Interestingly, a nucleotide insertion of c.1146 + 25insA in exon 6 was detected in five VSD patients, but not in 486 normal healthy controls. Our findings are useful in understanding the prevalence of GATA4 mutations and the correlation between the GATA4 genotype and the CHD phenotype in Chinese patients. (C) 2008 Elsevier Masson SAS. All rights reserved.