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Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease

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Abstract

CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

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Funding

This study was funded by Research Fund for the National Natural Science Foundation of China (No. 81260299, 81460282, 81470447), Doctoral Program of Higher Education of China (No. 20131107120020), and Basic Research Program of Qinghai Province (2017-ZJ-725).

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Author notes

  1. Shiming Liu and Zhaobing Su contribute equally to this manuscript.

Authors and Affiliations

  1. Qinghai High Altitude Medical Research Institute, No.7, Zhuanchang Road, West District, Xining, 810012, China

    Shiming Liu & Qiuhong Chen

  2. Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, 154 Humen Road, Humen, 523900, Guangdong, China

    Zhaobing Su & Jianmin Xiao

  3. Key Laboratory of Genetics and Birth Health of Hunan Province, Family Planning Institute of Hunan Province, Changsha, China

    Sainan Tan & Bin Ni

  4. Center for Genetics, National Research Institute for Family Planning, Beijing, 100081, China

    Hong Pan & Beihong Liu

  5. Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China

    Jing Wang

Authors
  1. Shiming Liu
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  2. Zhaobing Su
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  3. Sainan Tan
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  4. Bin Ni
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  5. Hong Pan
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  6. Beihong Liu
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  7. Jing Wang
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  8. Jianmin Xiao
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  9. Qiuhong Chen
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Corresponding authors

Correspondence to Jianmin Xiao or Qiuhong Chen.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Medical Ethics Committee of the Cardiovascular and Cerebrovascular Disease Hospital of Qinghai Province and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed written consents were obtained from all the participants.

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Liu, S., Su, Z., Tan, S. et al. Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease. Pediatr Cardiol 38, 1226–1231 (2017). https://doi.org/10.1007/s00246-017-1649-y

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  • DOI: https://doi.org/10.1007/s00246-017-1649-y

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