title: Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot.
abstract: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease             associated with significant morbidity and mortality in humans. However, the molecular             etiology underlying TOF in most patients remains largely unknown. In the present             study, sequence analysis of the GATA6 gene was performed from fresh-frozen cardiac             tissues and matched blood samples of 52 unrelated patients who underwent surgical             repair of TOF. The cardiac tissues and matched blood specimens from 46 patients             who underwent cardiac valve replacement due to rheumatic heart disease and blood             samples from 200 healthy individuals as controls were genotyped. The functional             characteristics of the mutations were assessed using a luciferase reporter assay             system. Based on the results, two novel heterozygous GATA6 mutations, p.G367X             and p.G394C, were identified in the cardiac tissues of 2 TOF patients, respectively.             No mutations were found in the cardiac tissues from 46 patients with rheumatic             heart disease and in the blood samples from the 298 participants. Functional analysis             demonstrated that the GATA6 mutants were consistently associated with significantly             reduced transcriptional activation compared with their wild-type counterpart.             This is the first report on the link of somatic GATA6 mutation to TOF, providing             novel insight into the molecular mechanism involved in TOF.
authors.affiliation: Department of Cardiothoracic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
authors.forename: Ri-Tai
authors.initials: RT
authors.lastname: Huang
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.forename: Ying-Jia
authors.initials: YJ
authors.lastname: Xu
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006321:Heart / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D013771:Tetralogy of Fallot / Q000235:genetics* / Q000503:physiopathology; D015533:Transcriptional Activation
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human