Abstract
IRX4 was the first identified cardiac transcription factor that is restricted to the ventricles at all stages of heart development. Irx4-deficient mice show ventricular dysfunction and develop cardiomyopathy. To study the potential impact of sequence variations in IRX4 on congenital heart disease (CHD) in humans, we examined the coding region of IRX4 in a cohort of 698 Chinese people with congenital heart disease and 250 healthy individuals as the controls. We found two potential disease-causing mutations, p. Asn85Tyr and p. Glu92Gly. A mammalian two-hybrid assay showed that both of the mutations significantly affected the interaction between IRX4 and RXRA. It demonstrated that IRX4 had a potential causative impact on the development of congenital heart disease, particularly ventricular septal defect.
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Acknowledgments
This work was supported by the National Basic Research Program of China (2010CB529505), the National Science and Technology Pillar Program of China (No.2008BAH24B05), the National Basic Research Program of China (2010CB529504) and the National Infrastructure Program of Chinese Genetic Resources (2006DKA21300).
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Z. Cheng and J. Wang contributed equally to the work.
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Cheng, Z., Wang, J., Su, D. et al. Two novel mutations of the IRX4 gene in patients with congenital heart disease. Hum Genet 130, 657–662 (2011). https://doi.org/10.1007/s00439-011-0996-7
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DOI: https://doi.org/10.1007/s00439-011-0996-7