title: Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation.
abstract: Familial recurrence of atrial fibrillation (AF) is reported in up to 15% of patients with lone AF. Recently, it was proposed that congenital defects in the morphogenesis of the pulmonary vein myocardium are involved in genetic pathogenesis of lone AF. GATA4 is a cardiac transcription factor essentially involved in myocardial development. Mutations in GATA4 are associated with congenital cardiac malformations. To investigate whether GATA4 mutations represent a genetic origin for AF the coding region of GATA4 was sequenced in 96 patients with lone AF. We found a GATA4 mutation (M247T) in a patient with familial lone AF and atrial septal aneurysm without interatrial shunts. The mutation affects a deeply conserved domain adjacent to the first zinc finger domain of GATA4 and was not reported before. A second GATA4 mutation (A411V) was found in a female patient with sporadic lone AF. This variant was previously reported in patients with cardiac septal defects. However, no anomalies of the atrial or ventricular septa were noted in the AF patient harboring A411V. We report for the first time that mutations in the cardiac transcription factor GATA4 may represent a genetic origin of lone AF. The study proposes that lone AF may share a common genetic origin with congenital cardiac malformations.
authors.affiliation: Experimental and Clinical Research Center (ECRC) at Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Maximilian G
authors.initials: MG
authors.lastname: Posch
authors.forename: Leif-Hendrik
authors.initials: LH
authors.lastname: Boldt
authors.forename: Michael
authors.initials: M
authors.lastname: Polotzki
authors.forename: Silke
authors.initials: S
authors.lastname: Richter
authors.forename: Sascha
authors.initials: S
authors.lastname: Rolf
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Rainer
authors.initials: R
authors.lastname: Dietz
authors.forename: Cemil
authors.initials: C
authors.lastname: Ozcelik
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Haverkamp
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D006343:Heart Septal Defects / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human