Article (Scientific journals)
ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects.
Izumi, Kosuke; Brett, Maggie; Nishi, Eriko et al.
2016In American Journal of Human Genetics, 99 (2), p. 451-9
Peer Reviewed verified by ORBi
 

Files


Full Text
Jacquinet AJHG.pdf
Publisher postprint (1.12 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
ARCN1-related syndrome; ER stress; exome sequencing; intracellular trafficking; microcephalic dwarfism; micrognathia; short stature
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Izumi, Kosuke
Brett, Maggie
Nishi, Eriko
Drunat, Severine
Tan, Ee-Shien
Fujiki, Katsunori
Lebon, Sophie
Cham, Breana
Masuda, Koji
Arakawa, Michiko
JACQUINET, Adeline ;  Centre Hospitalier Universitaire de Liège - CHU > Service de génétique
Yamazumi, Yusuke
Chen, Shu-Ting
Verloes, Alain
Okada, Yuki
Katou, Yuki
Nakamura, Tomohiko
Akiyama, Tetsu
Gressens, Pierre
Foo, Roger
Passemard, Sandrine
Tan, Ene-Choo
El Ghouzzi, Vincent
Shirahige, Katsuhiko
More authors (14 more) Less
Language :
English
Title :
ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects.
Publication date :
2016
Journal title :
American Journal of Human Genetics
ISSN :
0002-9297
eISSN :
1537-6605
Publisher :
University of Chicago Press, United States - Illinois
Volume :
99
Issue :
2
Pages :
451-9
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 16 January 2017

Statistics


Number of views
57 (1 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
 
49
Scopus citations®
without self-citations
43
OpenCitations
 
54

Bibliography


Similar publications



Contact ORBi