| First Author | Lindsay ME | Year | 2012 |
| Journal | Nat Genet | Volume | 44 |
| Issue | 8 | Pages | 922-7 |
| PubMed ID | 22772368 | Mgi Jnum | J:188799 |
| Mgi Id | MGI:5442244 | Doi | 10.1038/ng.2349 |
| Citation | Lindsay ME, et al. (2012) Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet 44(8):922-7 |
| abstractText | Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-beta signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-beta signaling, including either subunit of the TGF-beta receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-beta2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-beta signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-beta signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-beta signaling and phenotypic worsening in association with normalization of TGF-beta2 expression and high expression of TGF-beta1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-beta-mediated vasculopathies. |
