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RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease

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Abstract

Congenital heart disease (CHD) is the most frequent birth defect. RCAN1 (regulator of calcineurin 1) contributes to CHD in Down syndrome. However, whether RCAN1 is also associated with nonsyndromic CHD remains unclear. This study sequenced the exons and flanking region of RCAN1 in 128 sporadic CHD patients and 150 normal controls. We identified six novel heterozygous mutations in CHD patients. Functional assay showed that the g.482G>T could obviously raise the promoter activity of RCAN1.4 in vitro; However, we failed to detect the expression of RCAN1 in the right auricle, which made it confused to evaluate the pathogenicity of this mutation. In addition, we demonstrated that c.290T>C and g.1056+58C>A had no effect on the alternative splicing of RCAN1. The *196C>T, *790G>A, and *1278C>G did not influence the translation of RCAN1 post transcription. In conclusion, a novel mutation of g.482G>T in RCAN1 may be related to CHD by causing overexpression of RCAN1.4.

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Acknowledgements

The authors feel grateful to the children and parents involved in the study. This research was funded by Grant WX15A11 from Wuhan Municipal Planning Commission of Science and Research Fund. We would like to thank the great assistance from Dr. Chun Wu (Children’s Hospital of Chongqing Medical University).

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Authors and Affiliations

  1. Department of Cardiac Surgery, Cardiac Dynamics Laboratory, Wuhan Asia Heart Hospital, Wuhan, 430022, China

    Xiaoyong Li, Lei Shi, Ming Xu, Xun Zheng, Yiwen Yu & Jing Jin

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  1. Xiaoyong Li
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  2. Lei Shi
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  3. Ming Xu
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  4. Xun Zheng
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  5. Yiwen Yu
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Correspondence to Jing Jin.

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Ethical Approval

All authors state that this study complies with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study (written consent from parents and written assent from children).

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Li, X., Shi, L., Xu, M. et al. RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease. Pediatr Cardiol 39, 226–235 (2018). https://doi.org/10.1007/s00246-017-1746-y

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  • DOI: https://doi.org/10.1007/s00246-017-1746-y

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