Wei Ji1, Matthew A Benson2, Shoumo Bhattacharya2, Yiwei Chen1, Jingjing Hu1, Fen Li1. 1. Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. 2. Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
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.
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: F Zhao; C G Weismann; M Satoda; M E Pierpont; E Sweeney; E M Thompson; B D Gelb Journal: Am J Hum Genet Date: 2001-08-14 Impact factor: 11.025
Authors: S D Bamforth; J Bragança; J J Eloranta; J N Murdoch; F I Marques; K R Kranc; H Farza; D J Henderson; H C Hurst; S Bhattacharya Journal: Nat Genet Date: 2001-12 Impact factor: 38.330
Authors: José Bragança; Jyrki J Eloranta; Simon D Bamforth; J Claire Ibbitt; Helen C Hurst; Shoumo Bhattacharya Journal: J Biol Chem Date: 2003-02-12 Impact factor: 5.157
Authors: Jeff Reese; Nahid Waleh; Stanley D Poole; Naoko Brown; Christine Roman; Ronald I Clyman Journal: Pediatr Res Date: 2009-08 Impact factor: 3.756
Authors: Almira Zada; Laura E Kuil; Bianca M de Graaf; Naomi Kakiailatu; Jonathan D Windster; Alice S Brooks; Marjon van Slegtenhorst; Barbara de Koning; René M H Wijnen; Veerle Melotte; Robert M W Hofstra; Erwin Brosens; Maria M Alves Journal: Front Cell Dev Biol Date: 2022-07-08
Authors: Mohamed H Al-Sabri; Maryam Nikpour; Laura E Clemensson; Misty M Attwood; Michael J Williams; Mathias Rask-Anderson; Jessica Mwinyi; Helgi B Schiöth Journal: Cell Biosci Date: 2022-09-08 Impact factor: 9.584