Abstract
BackgroundThe occurrence of Congenital Heart Disease (CHD) is resulted from either genetic or environmental factors or the both. The CITED2 gene deletion or mutation is associated with the development of cardiac malformations. In this study, we have investigated the role of CITED2 gene mutation and methylation in the development of Congenital Heart Disease in pediatric patients in China.ResultsWe have screened 120 pediatric patients with congenital heart disease. Among these patients, 4 cases were detected to carry various CITED2 gene heterozygous mutations (c.550G > A, c.574A > G, c.573-578del6) leading correspondingly to the alterations of amino acid sequences in Gly184Ser, Ser192Gly, and Ser192fs, respectively. No CITED2 gene mutations were detected in the control group. At the same time, we found that CITED2 mutations could inhibit TFAP2c expression. In addition, we have demonstrated that abnormal CITED2 gene methylation was detected in most of the tested pediatric patients with CHD, which leads to a decrease of CITED2 transcription activities.ConclusionsOur study suggests that CITED2 gene mutations and methylation may play an important role in the development of pediatric congenital heart disease.
Highlights
The occurrence of Congenital Heart Disease (CHD) is resulted from either genetic or environmental factors or the both
CREB-binding protein (CBP)/P300-interacting transactivator 2 is a protein with ED-rich tail that in human is encoded by the CITED2 gene
Our study suggests that CITED2 gene mutations and methylation may play an important role in the development of pediatric congenital heart disease
Summary
The occurrence of Congenital Heart Disease (CHD) is resulted from either genetic or environmental factors or the both. We have investigated the role of CITED2 gene mutation and methylation in the development of Congenital Heart Disease in pediatric patients in China. A body of studies has demonstrated that the congenital heart diseases are caused by either genetic or environmental factors or both. Gene mutations are potential causes for the development of CHD [3], various environmental factors that affect mother during the pregnancy play an important role in promoting and developing of CHD [4]. There are a plurality of transcription factor binding sites in the promoter region of CITED2 gene, such as HIF-1, AP-2, SP1 etc., which play a vital role in CITED2 expression. Deficiencies in TFAP2 coactivation have been suggested to cause laterality defect in CITED2-/- mice [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
