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

被引：121

作者：

Schepers, Dorien ^{[1
,2
]}

Tortora, Giada ^{[3
,4
]}

Morisaki, Hiroko ^{[5
,6
,7
]}

MacCarrick, Gretchen ^{[8
]}

Lindsay, Mark ^{[9
]}

Liang, David ^{[10
]}

Mehta, Sarju G. ^{[11
]}

Hague, Jennifer ^{[11
]}

Verhagen, Judith ^{[12
]}

van de Laar, Ingrid ^{[12
]}

Wessels, Marja ^{[12
]}

Detisch, Yvonne ^{[13
]}

van Haelst, Mieke ^{[14
,15
]}

Baas, Annette ^{[14
]}

Lichtenbelt, Klaske ^{[14
]}

Braun, Kees ^{[16
]}

van der Linde, Denise ^{[17
]}

Roos-Hesselink, Jolien ^{[17
]}

McGillivray, George ^{[18
]}

Meester, Josephina ^{[1
,2
]}

Maystadt, Isabelle ^{[19
]}

Coucke, Paul ^{[20
,21
]}

El-Khoury, Elie ^{[22
]}

Parkash, Sandhya ^{[23
]}

Diness, Birgitte ^{[24
]}

Risom, Lotte ^{[24
]}

Scurr, Ingrid ^{[25
]}

Hilhorst-Hofstee, Yvonne ^{[26
]}

Morisaki, Takayuki ^{[5
,6
]}

Richer, Julie ^{[27
]}

Desir, Julie ^{[28
]}

Kempers, Marlies ^{[29
]}

Rideout, Andrea L. ^{[30
]}

Horne, Gabrielle ^{[31
,32
]}

Bennett, Chris ^{[33
]}

Rahikkala, Elisa ^{[34
]}

Vandeweyer, Geert ^{[1
,2
]}

Alaerts, Maaike ^{[1
,2
]}

Verstraeten, Aline ^{[1
,2
]}

Dietz, Hal ^{[8
]}

Van Laer, Lut ^{[1
,2
]}

Loeys, Bart ^{[1
,2
,29
]}

机构：

[1] Univ Antwerp, Ctr Med Genet, Antwerp, Belgium

[2] Antwerp Univ Hosp, Antwerp, Belgium

[3] Univ Bologna, Med Genet Unit, Policlin St Orsola Malpighi, Dept Med & Surg Sci, Bologna, Italy

[4] Marche Polytech Univ, Dept Mol & Clin Sci, Ancona, Italy

[5] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Biosci & Genet, Suita, Osaka, Japan

[6] Osaka Univ, Dept Mol Pathophysiol, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan

[7] Sakakibara Heart Inst, Dept Med Genet, Tokyo, Japan

[8] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[9] Harvard Med Sch, Dept Med & Pediat, Thorac Aortic Ctr, Massachusetts Gen Hosp, Boston, MA USA

[10] Stanford Univ, Med Ctr, Cardiovasc Med, Stanford, CA 94305 USA

[11] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, East Anglian Reg Genet Serv, Cambridge, England

[12] Erasmus Univ, Dept Clin Genet, Ctr Med, Rotterdam, Netherlands

[13] Maastricht Univ, Dept Clin Genet, Med Ctr, Maastricht, Netherlands

[14] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[15] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[16] Univ Med Ctr Utrecht, Dept Child Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands

[17] Erasmus MC, Dept Cardiol, Rotterdam, Netherlands

[18] Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Melbourne, Vic, Australia

[19] IPG, Ctr Genet Humaine, Gosselies, Charleroi, Belgium

[20] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[21] Univ Ghent, Ghent, Belgium

[22] Clin St Luc, Dept Diagnost Cardiol, Bouge, Namur, Belgium

[23] Dalhousie Univ, Dept Pediat, Maritime Med Genet Serv, IWK Hlth Ctr, Halifax, NS, Canada

[24] Copenhagen Univ Hosp, Dept Clin Genet, Rigshosp, Copenhagen, Denmark

[25] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England

[26] Leiden Univ, Dept Clin Genet, Med Ctr, Leiden, Netherlands

[27] Childrens Hosp Eastern Ontario, Res Inst, Dept Med Genet, Ottawa, ON, Canada

[28] Univ Libre Bruxelles, Ctr Genet Humaine, Hop Erasme, Brussels, Belgium

[29] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[30] IWK Hlth Ctr, Maritime Med Genet Serv, Halifax, NS, Canada

[31] Dalhousie Univ, Dept Med Cardiol, Halifax, NS, Canada

[32] Dalhousie Univ, Sch Biomed Engn, Halifax, NS, Canada

[33] Leeds Teaching Hosp NHS Trust, Dept Clin Genet, Chapel Allerton Hosp, Leeds, W Yorkshire, England

[34] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Oulu, Finland

来源：

HUMAN MUTATION | 2018年 / 39卷 / 05期

基金：

欧盟地平线“2020”;

关键词：

aneurysm; Loeys-Dietz syndrome; SMAD2; SMAD3; TGFB2; TGFB3; THORACIC AORTIC-ANEURYSM; LOEYS-DIETZ SYNDROME; GROWTH-FACTOR-BETA; LATENT TGF-BETA; MARFAN-SYNDROME; OSTEOARTHRITIS SYNDROME; MULTIPLE ANEURYSMS; SYNDROMIC FORM; MOUSE MODEL; RECEPTOR;

D O I：

10.1002/humu.23407

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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-beta (TGF-beta) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF-beta signaling. More recently, TGF-beta ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF-beta pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF-beta 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.

引用

页码：621 / 634

页数：14

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