ArticleHuman mutation2022
EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma.
Article in Human mutation, 2022. 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 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- Widening the Spectrum of Disease Expression due to Heterozygous Variants in EFEMP1.JAMA ophthalmology · 2026Article
- Large-Scaled Proteomics Analysis for Glaucoma: Integrated Genetics, Multi-Omics, UK Biobank and Therapeutic Analysis.Investigative ophthalmology & visual science · 2026Article
- Genetic Architecture and Clinical Phenotypes of Primary Open-Angle Glaucoma: An Updated Review of Mendelian Genes, GWAS Loci, and Polygenic Risk.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- Genetic Basis of Non-Syndromic Childhood Glaucoma Associated with Anterior Segment Dysgenesis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A spectrum of cysteine mutations in fibulin-3 highlight its disulfide bonding complexity and potential to induce ER stress.Scientific reports · 2025Article
- Progress in Translating Glaucoma Genetics Into the Clinic: A Review.Clinical & experimental ophthalmology · 2025Review
- EFEMP1 contributes to light-dependent ocular growth in zebrafish.Biology open · 2024Article
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.JCI insight · 2024Article
- Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Increasing the diagnostic yield of childhood glaucoma cases recruited into the 100,000 Genomes Project.BMC genomics · 2024Article
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma.Nature communications · 2024Article
- Multi-tissue transcriptome-wide association study identifies novel candidate susceptibility genes for cataract.Frontiers in ophthalmology · 2024Article
- Differences and Similarities Between Primary Open Angle Glaucoma and Primary Angle-Closure Glaucoma.Eye and brain · 2024Review
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.bioRxiv : the preprint server for biology · 2023Article
- Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Transcriptomic Analysis of the Ocular Posterior Segment Completes a Cell Atlas of the Human Eye.bioRxiv : the preprint server for biology · 2023Article
- Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).Journal of bone and mineral metabolism · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.
Indexed as
Identifiers
What OpenQuestion holds
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.