LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:

OpenAIRE is about to release its new face with lots of new content and services.
During September, you may notice downtime in services, while some functionalities (e.g. user registration, login, validation, claiming) will be temporarily disabled.
We apologize for the inconvenience, please stay tuned!
For further information please contact helpdesk[at]openaire.eu

fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Bertoli Avella, Aida; Gillis, Elisabeth; Morisaki, Hiroko; Verhagen, Judith; Graaf, Bianca; Van De Beek, Gerarda; Gallo, Elena; Kruithof, Boudewijn; Venselaar, Hanka; Myers, Loretha; Laga, Steven; Doyle, Alexander; Oswald, Gretchen; Cappellen, Gert; Yamanaka, Itaru; Helm, Robert; Beverloo, Berna; Klein, Annelies; Pardo Cortes, Luba; Lammens, Martin; Evers, Christina; Devriendt, Koenraad; Dumoulein, Michiel; Timmermans, Janneke; Brüggenwirth, Hennie; Verheijen, Frans; Rodrigus, Inez; Baynam, Gareth; Kempers, Marlies; Saenen, Johan ... view all 45 authors View less authors (2015)
Publisher: Elsevier BV
Journal: Journal of the American College of Cardiology
Languages: English
Types: Article
Subjects: LAP, latency-associated peptide, gene, TAAD, thoracic aortic aneurysms and dissections, Cardiology and Cardiovascular Medicine, LDS, Loeys-Dietz syndrome, SNP, single nucleotide polymorphism, MFS, Marfan syndrome, thoracic aortic aneurysm, Original Investigation, LOF, loss of function, TGFBR, transforming growth factor beta receptor, MIM, Mendelian Inheritance in Man, Loeys-Dietz syndrome, TGF, transforming growth factor, TGF-β pathway

Classified by OpenAIRE into

mesheuropmc: cardiovascular system
markdownabstractBACKGROUND Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-b signaling. OBJECTIVES This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. METHODS We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. RESULTS Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-b signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-b signaling in association with up-regulation of the expression of TGF-b ligands. CONCLUSIONS Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk.

Share - Bookmark

Funded by projects

  • NIH | MOLECULAR BIOLOGY OF THE MA...

Cite this article

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok