ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue American Journal of Human Genetics Année : 2016

ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects

Eriko Nishi
  • Fonction : Auteur
Ee-Shien Tan
  • Fonction : Auteur
Katsunori Fujiki
  • Fonction : Auteur
Breana Cham
  • Fonction : Auteur
Michiko Arakawa
  • Fonction : Auteur
Yusuke Yamazumi
  • Fonction : Auteur
Shu-Ting Chen
  • Fonction : Auteur
Alain Verloes
  • Fonction : Auteur
  • PersonId : 863600
Yuki Okada
  • Fonction : Auteur
Tomohiko Nakamura
  • Fonction : Auteur
Tetsu Akiyama
  • Fonction : Auteur
Roger Foo
  • Fonction : Auteur
Katsuhiko Shirahige
  • Fonction : co dernier-auteur
  • PersonId : 946516

Résumé

Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex. In this article, we report a clinically recognizable craniofacial disorder characterized by facial dysmorphisms, severe micrognathia, rhizomelic shortening, microcephalic dwarfism, and mild developmental delay due to loss-of-function heterozygous mutations in ARCN1, which encodes the coatomer subunit delta of COPI. ARCN1 mutant cell lines were revealed to have endoplasmic reticulum stress, suggesting the involvement of ER stress response in the pathogenesis of this disorder. Given that ARCN1 deficiency causes defective type I collagen transport, reduction of collagen secretion represents the likely mechanism underlying the skeletal phenotype that characterizes this condition. Our findings demonstrate the importance of COPI-mediated transport in human development, including skeletogenesis and brain growth.
Fichier principal
Vignette du fichier
Izumi, AJHG2016_Final version before copyright.pdf (1.6 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02859852 , version 1 (08-06-2020)

Identifiants

Citer

Kosuke Izumi, Maggie Brett, Eriko Nishi, Séverine Drunat, Ee-Shien Tan, et al.. ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects. American Journal of Human Genetics, 2016, 99 (2), pp.451-459. ⟨10.1016/j.ajhg.2016.06.011⟩. ⟨hal-02859852⟩
71 Consultations
58 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More