title: GATA5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient.
abstract: BACKGROUND
  GATA transcription factors are evolutionary conserved zinc finger proteins with multiple roles in cell differentiation/proliferation and organogenesis. GATA5 is only transiently expressed in the embryonic heart, and the inactivation of both Gata5 alleles results in a partially penetrant bicuspid aortic valve (BAV) phenotype in mice. We hypothesized that only biallelic mutations in GATA5 could be disease causing.
  
  
  METHODS
  A total of 185 patients with different forms of congenital heart disease (CHD) were screened along 150 healthy individuals for GATA4, 5, and 6. All patients' phenotypes were diagnosed with echocardiography.
  
  
  RESULTS
  Sequencing results revealed eight missense variants (three of which are novel) in cases with various conotruncal and septal defects. Out of these, two were inherited in recessive forms: the p.T67P variant, which was found both in patients and in healthy individuals, and the previously described p.Y142H variant which was only found in a patient with a double outlet right ventricle (DORV). We characterized the p.Y142H variant and showed that it significantly reduced the transcriptional activity of the protein over cardiac promoters by 30-40%.
  
  
  CONCLUSIONS
  Our results do prove that p.Y142H is associated with DORV and suggests including GATA5 as a potential gene to be screened in patients with this phenotype.
authors.affiliation: Department of Biochemistry and Molecular Genetics American University of Beirut Beirut Lebanon.
authors.forename: Kameel
authors.initials: K
authors.lastname: Kassab
authors.affiliation: Department of Biochemistry and Molecular Genetics American University of Beirut Beirut Lebanon.
authors.forename: Hadla
authors.initials: H
authors.lastname: Hariri
authors.affiliation: Department of Biochemistry University of Ottawa Ottawa Ontario Canada.
authors.forename: Lara
authors.initials: L
authors.lastname: Gharibeh
authors.affiliation: Department of Genetics Harvard Medical School and Department of Internal Medicine Massachusetts General Hospital Boston Massachusetts.
authors.forename: Akl C
authors.initials: AC
authors.lastname: Fahed
authors.affiliation: Department of Biochemistry and Molecular Genetics American University of Beirut Beirut Lebanon.
authors.forename: Manal
authors.initials: M
authors.lastname: Zein
authors.affiliation: Department of Biochemistry and Molecular Genetics American University of Beirut Beirut Lebanon.
authors.forename: Inaam
authors.initials: I
authors.lastname: El-Rassy
authors.affiliation: Department of Biochemistry University of Ottawa Ottawa Ontario Canada.
authors.forename: Mona
authors.initials: M
authors.lastname: Nemer
authors.affiliation: Department of Pediatrics and Adolescent Medicine American University of Beirut Beirut Lebanon.
authors.forename: Issam
authors.initials: I
authors.lastname: El-Rassi
authors.affiliation: Department of Biochemistry and Molecular GeneticsAmerican University of BeirutBeirutLebanon; Department of SurgeryAmerican University of BeirutBeirutLebanon.
authors.forename: Fadi
authors.initials: F
authors.lastname: Bitar
authors.affiliation: Department of Biochemistry and Molecular Genetics American University of Beirut Beirut Lebanon.
authors.forename: Georges
authors.initials: G
authors.lastname: Nemer
keywords: Congenital; GATA5; heart; homozygous; recessive; transcription