Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency.

Journal article

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: Ji, W; Benson, M; Bhattacharya, S; Chen, Y; Hu, J

• Publication status: Published
• Journal: Journal of surgical research
• Volume: 188
• Issue: 2
• Pages: 466-472
• Publication date: 2014-05-01
• DOI: 10.1016/j.jss.2014.01.015
• EISSN: 1095-8673
• ISSN: 0022-4804
• Language: English
• Keywords: Humans; Haploinsufficiency; Female; Mutation; Transcriptional Activation; Transcription Factor AP-2; Male; Ductus Arteriosus, Patent