Aperçu: G.M.
La
vitreoretinopathie exsudative familiale (FEVR) est un trouble de la cécité héréditaire caractérisé par le développement anormal du
système vasculaire de la rétine. La
majorité des mutations identifiées dans la FEVR se retrouvent dans
quatre gènes qui codent le complexe récepteur (FZD4, LRP5 et TSPAN12) et
le ligand (NPD) d'une voie moléculaire qui contrôle l'angiogenèse, la
voie de signalisation Norrin-β-catenin.
L'étude rapporte ici l'identification de mutations dans CTNNB1, le gène codant pour la β-caténine, comme cause de la FEVR.
Des
études antérieures ont signalé des mutations de CTNNB1 de novo
hétérozygotes comme cause d'une déficience intellectuelle syndromique
(ID) et d'un "trouble du spectre de l'autisme", et les mutations somatiques
sont liées à de nombreux cancers.
Am J Hum Genet. 2017 Jun 1;100(6):960-968. doi: 10.1016/j.ajhg.2017.05.001.
Defects in the Cell Signaling Mediator β-Catenin Cause the Retinal Vascular Condition FEVR
Panagiotou ES1, Sanjurjo Soriano C1, Poulter JA1, Lord EC1, Dzulova D1, Kondo H2, Hiyoshi A3, Chung BH4, Chu YW4, Lai CHY5, Tafoya ME6, Karjosukarso D7, Collin RWJ7, Topping J1, Downey LM8, Ali M1, Inglehearn CF1, Toomes C9.
Author information
- 1
- Section of Ophthalmology & Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK.
- 2
- Department of Ophthalmology, Fukuoka University, Fukuoka 814-0180, Japan; Department of Ophthalmology, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
- 3
- Department of Ophthalmology, Fukuoka University, Fukuoka 814-0180, Japan.
- 4
- Department of Paediatrics and Adolescent Medicine, Centre for Genomic Sciences, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
- 5
- Department of Ophthalmology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
- 6
- Pacific Retina Care, Waikele, HI 96797, USA.
- 7
- Department of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands.
- 8
- Section of Ophthalmology & Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK; Department of Ophthalmology, Hull Royal Infirmary, Hull HU3 2JZ, UK.
- 9
- Section of Ophthalmology & Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK. Electronic address: c.toomes@leeds.ac.uk
Abstract
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder
characterized by the abnormal development of the retinal vasculature.
The majority of mutations identified in FEVR are found within four genes
that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand
(NDP) of a molecular pathway that controls angiogenesis, the
Norrin-β-catenin signaling pathway. However, half of all FEVR-affected
case subjects do not harbor mutations in these genes, indicating that
further mutated genes remain to be identified. Here we report the
identification of mutations in CTNNB1, the gene encoding β-catenin, as a
cause of FEVR. We describe heterozygous mutations (c.2142_2157dup
[p.His720∗] and c.2128C>T [p.Arg710Cys]) in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs∗18])
in a simplex case subject. Previous studies have reported heterozygous
de novo CTNNB1 mutations as a cause of syndromic intellectual disability
(ID) and autism spectrum disorder,
and somatic mutations are linked to many cancers. However, in this
study we show that Mendelian inherited CTNNB1 mutations can cause
non-syndromic FEVR and that FEVR can be a part of the syndromic ID
phenotype, further establishing the role that β-catenin signaling plays
in the development of the retinal vasculature.
Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
- PMID: 28575650
- DOI: 10.1016/j.ajhg.2017.05.001
