Evidence map›Paper›PMID 40191993›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025

Non-coding single-nucleotide and structural variants affecting the EYS putative promoter cause autosomal recessive retinitis pigmentosa.

Tamar Hayman, Shai Ovadia, Jaya Krishnan, Manon Bouckaert, Daan M Panneman, Milton English, Johanna Valensi, Frans P M Cremers, Tamar Ben Yosef, L Ingeborgh van den Born and 8 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. The mutational and clinical spectrum ofFrontiers in genetics · 2026
    Article
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  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Tamar HaymanDivision of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shai OvadiaDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Jaya KrishnanNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Manon BouckaertCenter for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Daan M PannemanDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Milton EnglishNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Johanna ValensiDivision of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Frans P M CremersDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Tamar Ben YosefRuth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
L Ingeborgh van den BornThe Rotterdam Eye Hospital, Rotterdam, The Netherlands.
Suzanne E de BruijnDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Susanne RoosingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Eyal BaninDivision of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Samer KhatebDivision of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ruth Ashery-PadanNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Frauke CoppietersCenter for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
Anand SwaroopNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Dror SharonDivision of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: dror.sharon1@mail.huji.ac.il.

Funding

Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
Intramural NIH HHS ZIA EY000546
6 · The paper itself

Abstract

purposeVariants in untranslated genomic regions are difficult to identify as pathogenic but are capable of causing disease by interfering with gene expression. This study aimed to characterize the effect of variants identified in the 5'-untranslated region of EYS in patients with autosomal recessive retinitis pigmentosa (RP).

methodsVariant screening included gene panels, Sanger, exome, and genome sequencing. Functional validation included an electrophoretic mobility shift assay and various luciferase assays.

resultsPatients with RP from 6 EYS biallelic Arab-Muslim families harbored a 5' noncoding EYS variant, c.-453G>T, and 4 harbored a structural variant affecting the 5' noncoding exons. Electrophoretic mobility shift assay analysis revealed an effect on binding of transcription factors for c.-453G>T and a neighboring variant c.-454G>T. Dual luciferase assays using overexpression of various transcription factors showed distinct effects on expression. c.-453G>T was associated with higher luciferase expression with CRX overexpression and c.-454G>C with OTX2 overexpression. In addition, the 2 variants were found to influence translation by affecting upstream initiation codons. Interestingly, visual function of EYS RP patients who harbor c.-453G>T are better than those with biallelic null EYS variants.

conclusionOur analysis revealed both single-nucleotide and structural variants in the EYS promoter as the cause of autosomal recessive RP. These variants may affect EYS expression via a dual mechanism by altering transcription factor binding affinity at the EYS promoter and by affecting upstream open reading frames.

Indexed as

Eye ProteinsPromoter Regions, GeneticRetinitis Pigmentosa5' Untranslated RegionsAdultFemaleGenes, RecessiveGenetic Predisposition to DiseaseHumansMalePedigreePolymorphism, Single Nucleotide5' Untranslated RegionsEye ProteinsEYS protein, humanDisease-causing variantPhotoreceptorRegulatory elementRetinitis pigmentosaTranscription factor

Identifiers

PMID40191993
PMCPMC12969720

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Registered trials

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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.