Functionally significant, novel GATA4 variants are frequently associated with Tetralogy of Fallot

Human Mutation
Ritu DixitBhagyalaxmi Mohapatra

Abstract

Transcription factor GATA4 is known to play crucial role during heart development, regulating expression of several other key cardiogenic factors. Various GATA4 mutations are reported in familial as well as sporadic cases of congenital heart defects (CHDs). To estimate the prevalence and pathogenic potential of GATA4 variants in our CHD cohort, we have screened 285 CHD cases along with 200 controls by Sanger sequencing and identified 9 genetic variants (c.23C>A; p.Ala8Asp, c.25G>A; p.Ala9Thr, c.223G>T; p.Ala75Ser, c.383A>T; p.Glu128Val, c.397A>T; p.Ser133Cys, c.682T>A; p.Trp228Arg, c.1064C>G; p.Thr355Ser, c.1073G>C; p.Ser358Thr, and c.1220C>A; p.Pro407Gln) in 22 unrelated CHD probands (frequency:7.72%). Five of these are novel and located in the N-terminal transactivation domain (TAD) and first zinc finger domain. Majority C-terminal domain variants are polymorphic. Two of the TAD variants p.Glu128Val, p.Ser133Cys, and a first zinc finger variant p.Trp228Arg, impair combinatorial synergy of NKX2-5, SRF, and TBX5, suggesting potential role of these domains in GATA4 interactions with these factors. Decreased DNA-binding affinity with EMSA also supports this observation. Homology modeling and tertiary structure comparison show con...Continue Reading

References

Mar 28, 1997·The Journal of Biological Chemistry·E E MorriseyM S Parmacek
Jun 11, 1998·Developmental Genetics·D Durocher, M Nemer
Dec 18, 2001·American Journal of Medical Genetics·S J KennedyI Teshima
Jun 11, 2002·Journal of Molecular and Cellular Cardiology·Qiangrong Liang, Jeffery D Molkentin
Jul 9, 2002·Current Opinion in Genetics & Development·Roger K Patient, James D McGhee
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alistair J WattStephen A Duncan
Apr 6, 2005·American Journal of Medical Genetics. Part a·Kayoko Hirayama-YamadaRumiko Matsuoka
Aug 5, 2005·Development·Audrey Holtzinger, Todd Evans
Feb 14, 2006·Human Mutation·Georges NemerFadi Bitar
Mar 14, 2007·American Journal of Medical Genetics. Part a·Marie K SchlutermanVidu Garg
Jul 24, 2007·Journal of Molecular and Cellular Cardiology·Satish K RajagopalWilliam T Pu
Dec 7, 2007·Journal of Medical Genetics·A Tomita-MitchellE Goldmuntz
Dec 14, 2007·American Journal of Medical Genetics. Part a·Maximilian G PoschFelix Berger
Aug 2, 2008·European Journal of Medical Genetics·Weimin ZhangZhongzhi Li
Nov 17, 2009·Pediatric Cardiology·Ming-wu ChenTang-wei Liu
Mar 30, 2010·The Journal of Thoracic and Cardiovascular Surgery·Yu ChenDa-Yi Hu
Apr 7, 2010·European Journal of Medical Genetics·Maximilian G PoschWilhelm Haverkamp
Jul 28, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Ying ChenHong Li
Sep 30, 2010·Genetic Testing and Molecular Biomarkers·Tanya L ButlerDavid S Winlaw
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Diana LourençoAnu Bashamboo
Jun 3, 2011·Genetic Testing and Molecular Biomarkers·Sosalagere M DineshNallur B Ramachandra
Apr 1, 2010·Genetics and Molecular Biology·Marianna P R PortoAna Beatriz A Perez
Jun 29, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yi-Qing YangXu Liu
Jan 1, 2007·Indian Journal of Human Genetics·Smitha RamegowdaNallur B Ramachandra
Mar 28, 2012·Current Topics in Developmental Biology·Pingzhu ZhouWilliam T Pu
Apr 5, 2012·Molecular and Cellular Biology·Joseph M GallagherBranko V Latinkić
Apr 14, 2012·Circulation Journal : Official Journal of the Japanese Circulation Society·Kazuki KodoHiroyuki Yamagishi
May 4, 2012·Molecular Biology Reports·Jun WangYi-Qing Yang

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Citations

Sep 13, 2019·Genesis : the Journal of Genetics and Development·Zhengshan ZhaoGuoying Huang
Mar 12, 2021·Mutation Research·Manohar Lal YadavBhagyalaxmi Mohapatra
Jul 3, 2021·American Journal of Medical Genetics. Part a·Ritu DixitBhagyalaxmi Mohapatra

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