Homozygous loss-of-function mutations in ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
Homozygous loss-of-function mutations in ccdc134 are responsible for a severe form of osteogenesis imperfecta
Auteur(s) :
Dubail, Johanne [Auteur]
Brunelle, Perrine [Auteur]
Baujat, Genevieve [Auteur]
Huber, Celine [Auteur]
Doyard, Mathilde [Auteur]
Michot, Caroline [Auteur]
Chavassieux, Pascale [Auteur]
Khairouni, Abdeslam [Auteur]
Topouchian, Vicken [Auteur]
Monnot, Sophie [Auteur]
Koumakis, Eugenie [Auteur]
Cormier-Daire, Valerie [Auteur]
Brunelle, Perrine [Auteur]
Baujat, Genevieve [Auteur]
Huber, Celine [Auteur]
Doyard, Mathilde [Auteur]
Michot, Caroline [Auteur]
Chavassieux, Pascale [Auteur]
Khairouni, Abdeslam [Auteur]
Topouchian, Vicken [Auteur]
Monnot, Sophie [Auteur]
Koumakis, Eugenie [Auteur]
Cormier-Daire, Valerie [Auteur]
Titre de la revue :
Journal of bone and mineral research . the official journal of the American Society for Bone and Mineral Research
Nom court de la revue :
J. Bone Miner. Res.
Numéro :
35
Pagination :
1470-1480
Date de publication :
2020-04-14
ISSN :
0884-0431
Mot(s)-clé(s) :
OSTEOBLAST
CCDC134
MAPK PATHWAYS
OSTEOGENESIS IMPERFECTA
WHOLE-EXOME SEQUENCING
CCDC134
MAPK PATHWAYS
OSTEOGENESIS IMPERFECTA
WHOLE-EXOME SEQUENCING
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive ...
Lire la suite >Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). © 2020 American Society for Bone and Mineral Research.Lire moins >
Lire la suite >Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). © 2020 American Society for Bone and Mineral Research.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Collections :
Date de dépôt :
2021-09-02T07:02:26Z