title: Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency.
abstract: BACKGROUND
  Patent ductus arteriosus (PDA) is one of the most common congenital heart defects. Transcription factor AP-2 beta (TFAP2B) mutations are associated with the Char syndrome, a disorder associated with PDA, and with facial and fingers abnormalities. Recently, we identified two TFAP2B mutations in two families without Char syndrome phenotype, c.601+5G>A and c.435_438delCCGG, and these TFAP2B mutations were associated with familial isolated PDA. The aim of this study was to identify the effects of these mutations on TFAP2B function.
  
  
  METHODS
  Plasmids containing the wild-type or mutated TFAP2B were constructed and transfected in cells. Plasmids containing the TFAP2B coactivator, Cpb/p300-interacting transactivator 2 (CITED2), was also transfected. TFAP2B expression was detected by luciferase expression and by Western blot analysis.
  
  
  RESULTS
  These mutations resulted in loss of transactivation function, which could not be improved by Cpb/p300-interacting transactivator 2. The c.601+5G>A mutated gene did not express any protein, whereas the c.435_438delCCGG mutation did not impact the transactivation function activated by the wild-type TFAP2B.
  
  
  CONCLUSIONS
  These results suggest that a haploinsufficiency effect of TFAP2B could be involved in familial isolated PDA.
authors: Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Wei
authors: W
authors: Ji
authors: Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Matthew A
authors: MA
authors: Benson
authors: Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Shoumo
authors: S
authors: Bhattacharya
authors: Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Yiwei
authors: Y
authors: Chen
authors: Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Jingjing
authors: J
authors: Hu
authors: Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Fen
authors: F
authors: Li
mesh_terms: D004374:Ductus Arteriosus, Patent / Q000235:genetics*; D005260:Female; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D050656:Transcription Factor AP-2 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2
keywords: Haploinsufficiency; Mutation; Patent ductus arteriosus; TFAP2B