دورية أكاديمية
Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm
| العنوان: | Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm |
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| المؤلفون: | Doyle, A.J., Doyle, J.J., Bessling, S.L., Maragh, S., Lindsay, M.E., Schepers, D., Gillis, E., Mortier, G., Homfray, T., Sauls, K., Norris, R.A., Huso, N.D., Leahy, D., Mohr, D.W., Caulfield, M.J., Scott, A.F., Destree, A., Hennekam, R.C., Arn, P.H., Curry, C.J., Van Laer, L., McCallion, A.S., Loeys, B.L., Dietz, H.C. |
| المصدر: | Nature Genetics, 44, 11, pp. 1249-54 |
| سنة النشر: | 2012 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | IGMD 3: Genomic disorders and inherited multi-system disorders |
| الوصف: | Item does not contain fulltext ; Elevated transforming growth factor (TGF)-beta signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-beta signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-beta in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-beta activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-beta signaling cascades and higher expression of TGF-beta-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-beta signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/2066/108782Test; https://doi.org/10.1038/ng.2421Test |
| DOI: | 10.1038/ng.2421 |
| الإتاحة: | https://doi.org/10.1038/ng.2421Test http://hdl.handle.net/2066/108782Test |
| رقم الانضمام: | edsbas.C87BA422 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ng.2421 |
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