Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias

The term “fibrillinopathies” gathers various diseases with a wide spectrum of clinical features and severity but all share mutations in the fibrillin genes. The first described fibrillinopathy, Marfan syndrome (MFS), is a multisystem disease with a unique combination of skeletal, thoracic aortic ane...

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Autores principales:	Pauline Arnaud, Zakaria Mougin, Catherine Boileau, Carine Le Goff
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ADAMTS fibrillin-1 Marfan syndrome acromelic dysplasias extracellular matrix Genetics QH426-470
Acceso en línea:	https://doaj.org/article/26f0ccf8f98040f69f205ca8924d8b1e
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spelling	oai:doaj.org-article:26f0ccf8f98040f69f205ca8924d8b1e2021-12-01T13:26:08ZCooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias1664-802110.3389/fgene.2021.734718https://doaj.org/article/26f0ccf8f98040f69f205ca8924d8b1e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.734718/fullhttps://doaj.org/toc/1664-8021The term “fibrillinopathies” gathers various diseases with a wide spectrum of clinical features and severity but all share mutations in the fibrillin genes. The first described fibrillinopathy, Marfan syndrome (MFS), is a multisystem disease with a unique combination of skeletal, thoracic aortic aneurysm (TAA) and ocular features. The numerous FBN1 mutations identified in MFS are located all along the gene, leading to the same pathogenic mechanism. The geleophysic/acromicric dysplasias (GD/AD), characterized by short stature, short extremities, and joint limitation are described as “the mirror image” of MFS. Previously, in GD/AD patients, we identified heterozygous FBN1 mutations all affecting TGFβ-binding protein-like domain 5 (TB5). ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia. More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum. Together with human genetic data and generated knockout mouse models targeting the involved genes, we provide herein an overview of the role of fibrillin-1 in opposite phenotypes. Finally, we will decipher the potential biological cooperation of ADAMTS-fibrillin-1 involved in these opposite phenotypes.Pauline ArnaudPauline ArnaudZakaria MouginCatherine BoileauCatherine BoileauCarine Le GoffFrontiers Media S.A.articleADAMTSfibrillin-1Marfan syndromeacromelic dysplasiasextracellular matrixGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ADAMTS fibrillin-1 Marfan syndrome acromelic dysplasias extracellular matrix Genetics QH426-470
spellingShingle	ADAMTS fibrillin-1 Marfan syndrome acromelic dysplasias extracellular matrix Genetics QH426-470 Pauline Arnaud Pauline Arnaud Zakaria Mougin Catherine Boileau Catherine Boileau Carine Le Goff Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
description	The term “fibrillinopathies” gathers various diseases with a wide spectrum of clinical features and severity but all share mutations in the fibrillin genes. The first described fibrillinopathy, Marfan syndrome (MFS), is a multisystem disease with a unique combination of skeletal, thoracic aortic aneurysm (TAA) and ocular features. The numerous FBN1 mutations identified in MFS are located all along the gene, leading to the same pathogenic mechanism. The geleophysic/acromicric dysplasias (GD/AD), characterized by short stature, short extremities, and joint limitation are described as “the mirror image” of MFS. Previously, in GD/AD patients, we identified heterozygous FBN1 mutations all affecting TGFβ-binding protein-like domain 5 (TB5). ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia. More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum. Together with human genetic data and generated knockout mouse models targeting the involved genes, we provide herein an overview of the role of fibrillin-1 in opposite phenotypes. Finally, we will decipher the potential biological cooperation of ADAMTS-fibrillin-1 involved in these opposite phenotypes.
format	article
author	Pauline Arnaud Pauline Arnaud Zakaria Mougin Catherine Boileau Catherine Boileau Carine Le Goff
author_facet	Pauline Arnaud Pauline Arnaud Zakaria Mougin Catherine Boileau Catherine Boileau Carine Le Goff
author_sort	Pauline Arnaud
title	Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
title_short	Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
title_full	Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
title_fullStr	Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
title_full_unstemmed	Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias
title_sort	cooperative mechanism of adamts/ adamtsl and fibrillin-1 in the marfan syndrome and acromelic dysplasias
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/26f0ccf8f98040f69f205ca8924d8b1e
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Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias

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