Match!

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

Published on May 1, 2018in Human Mutation4.45
· 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)
Abstract
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
  • References (85)
  • Citations (10)
References85
Newest
#1Daiva Nevidomskyte (UW: University of Washington)H-Index: 2
#2Sherene Shalhub (UW: University of Washington)H-Index: 13
Last.Benjamin W. Starnes (UW: University of Washington)H-Index: 25
view all 7 authors...
#1Míriam Garcia-Bermúdez (Autonomous University of Barcelona)H-Index: 1
#2Abdel-Hakim Moustafa (Autonomous University of Barcelona)H-Index: 2
Last.Helena Tizón-Marcos (Autonomous University of Barcelona)H-Index: 1
view all 4 authors...
#1Dimitra Micha (VUmc: VU University Medical Center)H-Index: 8
#2Dongchuan Guo (University of Texas Health Science Center at Houston)H-Index: 32
Last.Hanka VenselaarH-Index: 29
view all 18 authors...
#1A. Blinc (University of Ljubljana)H-Index: 1
#2Aleš Maver (University of Ljubljana)H-Index: 9
Last.Borut Peterlin (University of Ljubljana)H-Index: 26
view all 7 authors...
#1Gabe Haller (UW: University of Washington)H-Index: 8
#2David M. Alvarado (UW: University of Washington)H-Index: 14
Last.Matthew B. Dobbs (UW: University of Washington)H-Index: 3
view all 10 authors...
#1Dorien Proost (University of Antwerp)H-Index: 4
#2Geert Vandeweyer (University of Antwerp)H-Index: 19
Last.Ronald V. Lacro (Boston Children's Hospital)H-Index: 28
view all 16 authors...
#1Christopher R. Burke (UW: University of Washington)H-Index: 2
#2Sherene Shalhub (UW: University of Washington)H-Index: 13
Last.Benjamin W. Starnes (UW: University of Washington)H-Index: 25
view all 3 authors...
Cited By10
Newest
#1Luc CozijnsenH-Index: 4
#2Astrid S. Plomp (UvA: University of Amsterdam)H-Index: 17
Last.Dimitra Micha (UvA: University of Amsterdam)
view all 10 authors...
#1Domenico Laterza (University of Modena and Reggio Emilia)H-Index: 1
#2Marco Ritelli (University of Brescia)H-Index: 15
Last.Chiara Vincenzi (University of Modena and Reggio Emilia)
view all 15 authors...
#1Norifumi Takeda (UTokyo: University of Tokyo)H-Index: 13
#2Norifumi Takeda (UTokyo: University of Tokyo)H-Index: 9
Last.Issei Komuro (UTokyo: University of Tokyo)H-Index: 88
view all 2 authors...
#1Katja Kloth (UHH: University of Hamburg)H-Index: 2
#2Tatjana Bierhals (UHH: University of Hamburg)H-Index: 6
Last.Kerstin Kutsche (UHH: University of Hamburg)H-Index: 31
view all 8 authors...
#1Ellen M. Hostetler (University of Texas Health Science Center at San Antonio)H-Index: 6
#2Ellen S. Regalado (University of Texas Health Science Center at San Antonio)H-Index: 24
Last.Stephanie Wallace (University of Texas Health Science Center at San Antonio)H-Index: 3
view all 17 authors...
View next paperQuantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity