A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3

Published on May 1, 2018in Human Mutation4.453
· DOI :10.1002/humu.23407
Dorien Schepers7
Estimated H-index: 7
(University of Antwerp),
Giada Tortora4
Estimated H-index: 4
(UNIBO: University of Bologna)
+ 39 AuthorsBart Loeys56
Estimated H-index: 56
(Radboud University Nijmegen)
The Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-β (TGF-β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF-β signaling. More recently, TGF-β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF-β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF-β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database. This article is protected by copyright. All rights reserved
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