Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency.
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 mutati...
| Huvudupphovsmän: | , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
| Publicerad: |
2014
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| _version_ | 1826256640753532928 |
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| author | Ji, W Benson, M Bhattacharya, S Chen, Y Hu, J Li, F |
| author_facet | Ji, W Benson, M Bhattacharya, S Chen, Y Hu, J Li, F |
| author_sort | Ji, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:05:27Z |
| format | Journal article |
| id | oxford-uuid:0146c18f-4d8e-4143-bff0-505bc4862592 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:05:27Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:0146c18f-4d8e-4143-bff0-505bc48625922022-03-26T08:34:06ZCharacterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0146c18f-4d8e-4143-bff0-505bc4862592EnglishSymplectic Elements at Oxford2014Ji, WBenson, MBhattacharya, SChen, YHu, JLi, FBACKGROUND: 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. |
| spellingShingle | Ji, W Benson, M Bhattacharya, S Chen, Y Hu, J Li, F Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title | Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title_full | Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title_fullStr | Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title_full_unstemmed | Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title_short | Characterization of transcription factor AP-2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency. |
| title_sort | characterization of transcription factor ap 2 β mutations involved in familial isolated patent ductus arteriosus suggests haploinsufficiency |
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