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Nakanishi T, Markwald RR, Baldwin HS, et al., editors. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology [Internet]. Tokyo: Springer; 2016. doi: 10.1007/978-4-431-54628-3_54

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Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology [Internet].

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Chapter 54To Detect and Explore Mechanism of CITED2 Mutation and Methylation in Children with Congenital Heart Disease

, M.D., Ph.D., , , , and .

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Published online: June 25, 2016.

In this study we found four CITED2 coding region mutations (c.550G>A, c.574A>G, c.573–578del6) which led to alterations of amino acid sequence (p.Gly184Ser, p.Ser192Gly, p.Ser192fs) in 120 children with congenital heart disease. The CITED2 mutation associated with the dysregulation of HIF-1α, TFAP2c, and CITED2 methylation accompanied with its decrease in mRNA expression might be involved in the pathological process of congenital heart disease.

Keywords:

CITED2, Mutation, Methylation, Congenital heart disease

CITED2 mutation and methylation may be the cause of CHD. The purpose of this study was (1) to identify CITED2 mutation in children with CHD in China, (2) to analyze the mechanism of CITED2 mutation in cellular level if CITED2 gene mutation affects expression of HIF-1α and TFAP2c, and (3) to examine if CITED2 CpG island methylation exists in children with congenital heart disease.

1.

Four CITED2 coding region mutations (c.550G>A one case, c.574A>G one case, c.573–578del6 two cases) exist in 120 children with congenital heart disease (Fig. 54.1) [1].

2.

CITED2 mutation can inhibit TFAP2c expression. Our study also demonstrated that CITED2 has negative inhibition for HIF-1α. But this negative mechanism will be weakened owing to CITED2 mutation in congenital heart disease; HIF-1α expression was elevated in CITED2 mutant group.

3.

The CITED2 methylation is another mechanism of promoting congenital heart disease. CITED2 abnormal methylation was found in 26 of 31 congenital heart diseases. The abnormal methylation leads to decreased CITED2 mRNA expression [2].

Fig. 54.1

Fig. 54.1

The sequence of CITED2 mutation

CITED2 mutation and methylation may play an important role for the development of congenital heart disease.

References

1.
Yang XF, Wu XY, Li M, et al. Mutation analysis of Cited2 in patients with congenital heart disease [J]. Zhonghua Er Ke Za Zhi. 2010;48(4):293–6. [PubMed: 20654020]
2.
Xu M, Wu XY, Li YG, et al. Relationship of CpG islands methylation of CITED2 and congenital heart disease [J]. Third Mil Med Univ. 2013;35(3):245–6.
Copyright 2016, The Author(s)

Open Access This chapter is distributed under the terms of the Creative Commons Attribution-Noncommercial 2.5 License (http://creativecommons.org/licenses/by-nc/2.5/), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. The images or other third party material in this chapter are included in the work's Creative Commons license, unless indicated otherwise in the credit line; if such material is not included in the work's Creative Commons license and the respective action is not permitted by statutory regulation, users will need to obtain permission from the license holder to duplicate, adapt or reproduce the material.

Bookshelf ID: NBK500255PMID: 29787114DOI: 10.1007/978-4-431-54628-3_54
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