Kondo Hiroyuki
   Department   School of Medicine  Ophthalmology, Clinical Medical Sciences
Article types case reports
Language English
Peer review Peer reviewed
Title Defects in the Cell Signaling Mediator β-Catenin Cause the Retinal Vascular Condition FEVR.
Journal Formal name:American journal of human genetics
Abbreviation:Am J Hum Genet
ISSN code:15376605/00029297
Domestic / ForeginForegin
Volume, Issue, Page 100(6),960-968頁
Author and coauthor Panagiotou Evangelia S, Sanjurjo Soriano Carla, Poulter James A, Lord Emma C, Dzulova Denisa, Kondo Hiroyuki, Hiyoshi Atsushi, Chung Brian Hon-Yin, Chu Yoyo Wing-Yiu, Lai Connie H Y, Tafoya Mark E, Karjosukarso Dyah, Collin Rob W J, Topping Joanne, Downey Louise M, Ali Manir, Inglehearn Chris F, Toomes Carmel
Publication date 2017/06
Summary 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.
DOI 10.1016/j.ajhg.2017.05.001
PMID 28575650