Open AccessGATA 5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient
Author(s) -
Kassab Kameel,
Hariri Hadla,
Gharibeh Lara,
Fahed Akl C.,
Zein Manal,
ElRassy Inaam,
Nemer Mona,
ElRassi Issam,
Bitar Fadi,
Nemer Georges
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.190
Subject(s) - missense mutation , phenotype , heart development , medicine , genetics , gata4 , bicuspid aortic valve , allele , mutation , gene , heart disease , ventricle , double outlet right ventricle , zinc finger , biology , transcription factor , embryonic stem cell , aortic valve
Abstract Background GATA transcription factors are evolutionary conserved zinc finger proteins with multiple roles in cell differentiation/proliferation and organogenesis. GATA 5 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 GATA 5 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 GATA 4, 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%. Conclusion Our results do prove that p.Y142H is associated with DORV and suggests including GATA 5 as a potential gene to be screened in patients with this phenotype.