Abstract
Although the etiology for the majority of congenital heart disease (CHD) remains poorly understood, the known genetic causes are often the result of mutations in cardiac developmental genes. GATA6 encodes for a cardiac transcription factor, which is broadly expressed in the developing heart and is critical for normal cardiac morphogenesis, making it a candidate gene for congenital heart defects in humans. The objective of this study was to determine the frequency of GATA6 sequence variants in a population of individuals with a spectrum of cardiac malformations. The coding regions of GATA6 were sequenced in 310 individuals with CHD. We identified two novel sequence variations in GATA6 that altered highly conserved amino acid residues (A178V and L198V) and were not found in a control population. These variants were identified in two individuals (one with tetralogy of Fallot and the other with an atrioventricular septal defect in the setting of complex CHD). Biochemical studies demonstrate that the GATA6 A178V mutant protein results in increased transactivation ability when compared with wild-type GATA6. These data suggest that nonsynonymous GATA6 sequence variants are infrequently found in individuals with CHD.
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Abbreviations
- α-MHC:
-
alpha-myosin heavy chain
- ANF:
-
atrial natriuretic factor
- CHD:
-
congenital heart disease
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Acknowledgements
We thank the families for their participation; C. Rains, J. Neumann, and A. Winborn for research coordinator support; C. Turner for technical support; members of the McDermott Center for Human Growth and Development for assistance with sequencing; the Divisions of Pediatric Cardiology and Pediatric Cardiothoracic Surgery at Children's Medical Center of Dallas for assistance with clinical information and management; and Dr. K.L. McBride for critical review of the article.
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Supported by Grants NIH/NHLBI (R01HL080592 and R01HL057181) and California Institute for Regenerative Medicine (to D.S.) and by Grants NIH/NHLBI (R01HL088965) and the Children's Heart Foundation (to V.G.).
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Maitra, M., Koenig, S., Srivastava, D. et al. Identification of GATA6 Sequence Variants in Patients With Congenital Heart Defects. Pediatr Res 68, 281–285 (2010). https://doi.org/10.1203/PDR.0b013e3181ed17e4
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DOI: https://doi.org/10.1203/PDR.0b013e3181ed17e4
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