Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta
Mathilde Huckert
(1, 2)
,
Corinne Stoetzel
(1, 3)
,
Supawich Morkmued
(4, 5)
,
Virginie Laugel-Haushalter
(4)
,
Véronique Geoffroy
(1, 3)
,
Jean Muller
(4, 6, 2)
,
François Clauss
(7, 2)
,
Megana Prasad
(1, 3)
,
Frédéric Obry
(8, 2)
,
Jean Louis Raymond
(8)
,
Marzena Switala
(8, 2)
,
Yves Alembik
(2)
,
Sylvie Soskin
(2)
,
Eric Mathieu
(9)
,
Joseph Hemmerlé
(9)
,
Jean-Luc Weickert
(4)
,
Branka Brukner Dabovic
(10)
,
Daniel Rifkin
(10)
,
Annelies Dheedene
(11, 12)
,
Eveline Boudin
(13, 14)
,
Oana Caluseriu
(15, 16)
,
Marie-Claude Cholette
(15, 16)
,
Ross Mcleod
(15, 16)
,
Reynaldo Antequera
(17)
,
Marie-Paule Gellé
(18)
,
Jean-Louis Coeuriot
(19)
,
Louis-Frédéric Jacquelin
(19)
,
Isabelle Bailleul-Forestier
(20, 21)
,
Marie-Cécile Manière
(2, 8)
,
Wim van Hul
(13, 14)
,
Debora Bertola
(22)
,
Pascal Dollé
(4)
,
Alain Verloes
(23)
,
Geert Mortier
(11, 12, 13, 14)
,
Hélène Dollfus
(1, 3, 2)
,
Agnès Bloch-Zupan
(1, 3)
1
LGM -
Laboratoire de Génétique Médicale
2 HUS - Les Hôpitaux Universitaires de Strasbourg
3 FMTS - Fédération de Médecine Translationnelle de Strasbourg
4 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
5 KKU - Khon Kaen University [Thailand]
6 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
7 IRM - Immuno-Rhumatologie Moléculaire
8 UNISTRA - Université de Strasbourg
9 BB - Biomatériaux et Bioingénierie
10 NYU Langone Medical Center - New York University Langone Medical Center
11 UGENT - Universiteit Gent = Ghent University = Université de Gand
12 Ghent University Hospital
13 UA - University of Antwerp
14 UZA - Antwerp University Hospital [Edegem]
15 University of Calgary
16 ACHRI - Alberta Children's Hospital Research Institute
17 FMUSP - Faculdade de Medicina da Universidade de São Paulo
18 BIOS - Biomatériaux et inflammation en site osseux - EA 4691
19 URCA - Université de Reims Champagne-Ardenne
20 UT3 - Université Toulouse III - Paul Sabatier
21 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
22 USP - Universidade de São Paulo = University of São Paulo
23 Hôpital Robert Debré
2 HUS - Les Hôpitaux Universitaires de Strasbourg
3 FMTS - Fédération de Médecine Translationnelle de Strasbourg
4 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
5 KKU - Khon Kaen University [Thailand]
6 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
7 IRM - Immuno-Rhumatologie Moléculaire
8 UNISTRA - Université de Strasbourg
9 BB - Biomatériaux et Bioingénierie
10 NYU Langone Medical Center - New York University Langone Medical Center
11 UGENT - Universiteit Gent = Ghent University = Université de Gand
12 Ghent University Hospital
13 UA - University of Antwerp
14 UZA - Antwerp University Hospital [Edegem]
15 University of Calgary
16 ACHRI - Alberta Children's Hospital Research Institute
17 FMUSP - Faculdade de Medicina da Universidade de São Paulo
18 BIOS - Biomatériaux et inflammation en site osseux - EA 4691
19 URCA - Université de Reims Champagne-Ardenne
20 UT3 - Université Toulouse III - Paul Sabatier
21 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
22 USP - Universidade de São Paulo = University of São Paulo
23 Hôpital Robert Debré
Véronique Geoffroy
- Fonction : Auteur
- PersonId : 1055359
- IdHAL : veronique-geoffroy
- ORCID : 0000-0002-4149-0857
Marzena Switala
- Fonction : Auteur
Marie-Paule Gellé
- Fonction : Auteur
- PersonId : 1118690
- ORCID : 0000-0003-1569-7085
- IdRef : 05940499X
Résumé
Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.
Domaines
Génétique| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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