To Detect and Explore Mechanism of CITED2 Mutation and Methylation in Children with Congenital Heart Disease
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.
KeywordsCITED2 Mutation Methylation Congenital heart disease
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.
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 .
CITED2 mutation and methylation may play an important role for the development of congenital heart disease.
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