ArticleThe Journal of clinical investigation2021
Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Computational Quantification of Mouse Retinal Vasculature Using ImageJ.Bio-protocol · 2026Article
- KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy by inhibiting phosphorylation-driven PRDX1 phase separation.Nature communications · 2026Article
- Analysis of familial exudative vitreoretinopathy (FEVR) cases in the UK 100 000 genomes project increases diagnostic rate and implicates heterozygousJournal of medical genetics · 2026Article
- A novel variant p.Y250C of FZD4 influences Norrine/β-catenin signaling pathway that associates with familial exudative vitreoretinopathy (FEVR).Scientific reports · 2026Article
- Targeting Diabetic Retinopathy with Human iPSC-Derived Vascular Reparative Cells in a Type 2 Diabetes Model.Cells · 2025Article
- CTNNB1 syndrome mouse models.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Hereditary Vitreoretinopathies: Molecular Diagnosis, Clinical Presentation and Management.Clinical & experimental ophthalmology · 2025Review
- Novel compound heterozygous OBSCN variants in Chinese children with congenital pulmonary airway malformation.Italian journal of pediatrics · 2025Article
- Clinical and genetic characteristics and natural history of Finnish families with familial exudative vitreoretinopathy due to pathogenic FZD4 variants.Acta ophthalmologica · 2025Article
- Gene Variant Spectrum in Probands With Familial Exudative Vitreoretinopathy Using an Expanded Panel.Investigative ophthalmology & visual science · 2025Article
- Norrin in cancer: from a promising prognostic biomarker to a novel therapeutic target.Frontiers in oncology · 2025Review
- Mechanistic study of the hsa_circ_0074158 binding EIF4A3 impairing sepsis-induced endothelial barrier.Frontiers in immunology · 2025Article
- Article
- Rescue of cochlear vascular pathology prevents sensory hair cell loss in Norrie disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Identification of LRRC46 as a novel candidate gene for high myopia.Science China. Life sciences · 2024Article
- Review
- CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Multimodal imaging of white preretinal lesions in atypical familial exudative vitreoretinopathy: Case report and literature review.American journal of ophthalmology case reports · 2024Article
- Identification of Novel FZD4 Mutations in Familial Exudative Vitreoretinopathy and Investigating the Pathogenic Mechanisms of FZD4 Mutations.Investigative ophthalmology & visual science · 2024Article
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Familial exudative vitreoretinopathy (FEVR) is a severe retinal vascular disease that causes blindness. FEVR has been linked to mutations in several genes associated with inactivation of the Norrin/β-catenin signaling pathway, but these account for only approximately 50% of cases. We report that mutations in α-catenin (CTNNA1) cause FEVR by overactivating the β-catenin pathway and disrupting cell adherens junctions. We identified 3 heterozygous mutations in CTNNA1 (p.F72S, p.R376Cfs*27, and p.P893L) by exome sequencing and further demonstrated that FEVR-associated mutations led to overactivation of Norrin/β-catenin signaling as a result of impaired protein interactions within the cadherin-catenin complex. The clinical features of FEVR were reproduced in mice lacking Ctnna1 in vascular endothelial cells (ECs) or with overactivated β-catenin signaling by an EC-specific gain-of-function allele of Ctnnb1. In isolated mouse lung ECs, both CTNNA1-P893L and F72S mutants failed to rescue either the disrupted F-actin arrangement or the VE-cadherin and CTNNB1 distribution. Moreover, we discovered that compound heterozygous Ctnna1 F72S and a deletion allele could cause a similar phenotype. Furthermore, in a FEVR family, we identified a mutation of LRP5, which activates Norrin/β-catenin signaling, and the corresponding knockin mice exhibited a partial FEVR-like phenotype. Our study demonstrates that the precise regulation of β-catenin activation is critical for retinal vascular development and provides new insights into the pathogenesis of FEVR.
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