title: Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Cuimei
authors.initials: C
authors.lastname: Zhang
authors.forename: Youming
authors.initials: Y
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wei
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Wanjun
authors.initials: W
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Xuan
authors.initials: X
authors.lastname: Shang
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D005787:Gene Frequency; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D012307:Risk Factors; D017386:Sequence Homology, Amino Acid; D050656:Transcription Factor AP-2 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors