title: Novel GATA4 mutations in lone atrial fibrillation.
abstract: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and is             a major cause of morbidity and mortality. Previous studies have established genetic             defects as a risk factor for AF in a minority of patients. However, AF is of substantial             genetic heterogeneity and the molecular determinants for AF in a majority of cases             remain unclear. In this study, the entire coding sequence and splice junctions             of GATA4, which encodes a zinc-finger transcription factor essential for cardiogenesis,             were sequenced in 160 unrelated patients with lone AF. A total of 200 unrelated             ethnically matched healthy individuals were used as controls. The available relatives             of the patient carrying an identified mutation were genotyped. The functional             characteristics of the mutant GATA4 were analyzed using a luciferase reporter             assay system. As a result, two novel heterozygous GATA4 mutations of p.G16C and             p.H28D, were identified in 2 unrelated families with AF, respectively, which co-segregated             with AF in each family with complete penetrance. Functional analysis demonstrated             that the mutations of GATA4 were associated with a significantly decreased transcriptional             activity. The findings expand the mutation spectrum of GATA4 linked to AF and             provide novel insight into the molecular mechanism involved in the pathogenesis             of AF.
authors.affiliation: Department of Emergency, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200030, PR China.
authors.forename: Jin-Qi
authors.initials: JQ
authors.lastname: Jiang
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Shen
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Fang
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D019556:COS Cells; D016022:Case-Control Studies; D002522:Chlorocebus aethiops; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D017930:Genes, Reporter; D006579:Heterozygote; D006801:Humans; D008156:Luciferases / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010957:Plasmids; D014162:Transfection
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D008156:Luciferases