ArticleExperimental eye research2014
Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the oligomerization, of Bestrophin-1.
Article in Experimental eye research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Allele-specific suppression of pathogenic bestrophin-1 transcripts by CRISPR/Cas9-mediated genome editing.Genome medicine · 2026Article
- From BEST1 mutations to retinal regeneration: integrating stem cell-derived RPE models and gene correction strategies.Frontiers in cell and developmental biology · 2026Review
- Novel BEST1 Variant Characterization in a Large French Cohort in Light of Updated Bestrophin-1 Structure-Function Correlation.Investigative ophthalmology & visual science · 2025Article
- A spontaneous nonhuman primate model of inherited retinal degeneration.JCI insight · 2025Article
- Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing.Current medical science · 2024Article
- Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.International journal of molecular sciences · 2022Article
- Clinical findings in eyes with BEST1-related retinopathy complicated by choroidal neovascularization.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Observational
- Article
- Long-Range PCR-Based NGS Applications to Diagnose Mendelian Retinal Diseases.International journal of molecular sciences · 2021Article
- Sensing through Non-Sensing Ocular Ion Channels.International journal of molecular sciences · 2020Review
- Human iPSC Modeling Reveals Mutation-Specific Responses to Gene Therapy in a Genotypically Diverse Dominant Maculopathy.American journal of human genetics · 2020Article
- Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies.International journal of molecular sciences · 2020Article
- Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction.Frontiers in cell and developmental biology · 2020Review
- The Y227N mutation affects bestrophin-1 protein stability and impairs sperm function in a mouse model of Best vitelliform macular dystrophy.Biology open · 2019Article
- Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients.Scientific reports · 2018Article
- Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing.Scientific reports · 2018Article
- BEST1 protein stability and degradation pathways differ between autosomal dominant Best disease and autosomal recessive bestrophinopathy accounting for the distinct retinal phenotypes.Human molecular genetics · 2018Article
- Mutant Best1 Expression and Impaired Phagocytosis in an iPSC Model of Autosomal Recessive Bestrophinopathy.Scientific reports · 2018Article
- Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy.Scientific reports · 2017Article
- Bestrophin 1 and retinal disease.Progress in retinal and eye research · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BEST1 encodes Bestrophin-1 (Best1), a homo-oligomeric, integral membrane protein localized to the basolateral plasma membrane of the retinal pigment epithelium. Mutations in BEST1 cause five distinct retinal degenerative diseases, including adult vitelliform macular dystrophy (AVMD), autosomal recessive bestrophinopathy (ARB), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and retinitis pigmentosa (RP). The mechanisms underlying these diseases and why mutations cause one disease over another are, for the most part, unknown. To gain insights into these four diseases, we expressed 28 Best1 mutants fused to YFP in polarized MDCK monolayers and, via confocal microscopy and immunofluorescence, live-cell FRET, and reciprocal co-immunoprecipitation experiments, screened these mutants for defects in localization and oligomerization. All 28 mutants exhibited comparable FRET efficiencies to and co-immunoprecipitated with WT Best1, indicating unimpaired oligomerization. RP- and ADVIRC-associated mutants were properly localized to the basolateral plasma membrane of cells, while two AVMD and most ARB mutants were mislocalized. When co-expressed, all mislocalized mutants caused mislocalization of WT Best1 to intracellular compartments. Our current and past results indicate that mislocalization of Best1 is not an absolute feature of any individual bestrophinopathy, occurring in AVMD, BVMD, and ARB. Furthermore, some ARB mutants that do not also cause dominant disease cause mislocalization of Best1, indicating that mislocalization is not a cause of disease, and that absence of Best1 activity from the plasma membrane is tolerated. Lastly, we find that the ARB truncation mutants L174Qfs*57 and R200X can form oligomers with WT Best1, indicating that the first ∼174 amino acids of Best1 are sufficient for oligomerization to occur.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.