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

Pediatr Cardiol. 2017 Aug;38(6):1226-1231. doi: 10.1007/s00246-017-1649-y. Epub 2017 Jul 8.


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.

Keywords: CITED2; Chinese Tibetan population; Congenital heart disease (CHD); Mutation; VEGF.

MeSH terms

  • Adolescent
  • Asian Continental Ancestry Group
  • Child
  • China / ethnology
  • Ductus Arteriosus, Patent / genetics
  • Female
  • Heart / embryology
  • Heart Defects, Congenital / genetics*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Mutation
  • Repressor Proteins / genetics*
  • Tibet
  • Trans-Activators / genetics*
  • Vascular Endothelial Growth Factor A / metabolism


  • CITED2 protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Repressor Proteins
  • Trans-Activators
  • Vascular Endothelial Growth Factor A