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Two novel mutations of the IRX4 gene in patients with congenital heart disease

Human Genetics volume 130, pages 657–662 (2011)Cite this article

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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Affiliations

  1. Center for Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing, 100081, China

    Zhi Cheng, Jing Wang, Dongmei Su, Hong Pan, Binbin Wang & Xu Ma

  2. World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, China

    Xu Ma

  3. Graduate School, Peking Union Medical College, Beijing, China

    Zhi Cheng, Jing Wang, Binbin Wang & Xu Ma

  4. Pediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, China

    Guoying Huang & Xiaotian Li

  5. Public Central Laboratory, Beijing Pediatric Institute, Beijing Children’s Hospital affiliated to Capital Medical University, Beijing, China

    Zhongzhi Li & Adong Shen

  6. School of Life Science, Lanzhou University, Lanzhou, China

    Xiaodong Xie

Authors
  1. Zhi Cheng
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  2. Jing Wang
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  3. Dongmei Su
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  4. Hong Pan
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  5. Guoying Huang
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  6. Xiaotian Li
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  7. Zhongzhi Li
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  8. Adong Shen
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  9. Xiaodong Xie
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  10. Binbin Wang
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  11. Xu Ma
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Corresponding authors

Correspondence to Binbin Wang or Xu Ma.

Additional information

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

Keywords

  • Congenital Heart Disease
  • Ventricular Septal Defect
  • Ventricular Septal Defect
  • Congenital Heart Disease Patient
  • IRX4 Gene