Evidence map›Paper›PMID 33067476›Full record

ArticleScientific reports2020

Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration.

Almudena Sacristan-Reviriego, Hoang Mai Le, Michalis Georgiou, Isabelle Meunier, Beatrice Bocquet, Anne-Françoise Roux, Chrisostomos Prodromou, James Bainbridge, Michel Michaelides, Jacqueline van der Spuy

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Restoring Sight: The Journey of AIPL1 from Discovery to Therapy.International journal of molecular sciences · 2025
    Review
  2. Computational Evidence for Digenic Contribution ofInternational journal of molecular sciences · 2025
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Zebrafish models of inherited retinal dystrophies.Journal of translational genetics and genomics · 2022
    Article
  11. Review
  12. Article
  13. Review
  14. Review
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

10 authors at 5 institutions in 2 countries.

Almudena Sacristan-ReviriegoUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK.
Hoang Mai LeUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK.
Michalis GeorgiouUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK.
Isabelle MeunierCentre National de Référence Maladies Sensorielles Génétiques, Service Ophtalmologie Hôpital Gui de Chauliac - CHRU de Montpellier, 80 rue Augustin Fliche, 34295, Montpellier, France.
Beatrice BocquetCentre National de Référence Maladies Sensorielles Génétiques, Service Ophtalmologie Hôpital Gui de Chauliac - CHRU de Montpellier, 80 rue Augustin Fliche, 34295, Montpellier, France.
Anne-Françoise RouxLaboratoire de Génétique Moléculaire, CHU de Montpellier, Université de Montpellier, Montpellier, France.
Chrisostomos ProdromouBiochemistry and Biomedicine, University of Sussex, Brighton, Falmer, BN1 9QG, UK.
James BainbridgeUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK.
Michel MichaelidesUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK.
Jacqueline van der SpuyUCL Institute of Ophthalmology, University College London, 11 - 43 Bath Street, London, EC1V 9EL, UK. j.spuy@ucl.ac.uk.
University College London · GBHôpital Gui de Chauliac · FRMoorfields Eye Hospital NHS Foundation Trust · GBInstitut de Génétique Moléculaire de Montpellier · FRUniversity of Sussex · GB

Funding

Medical Research Council MR/P02582X/1
6 · The paper itself

Abstract

Disease-causing sequence variants in the highly polymorphic AIPL1 gene are associated with a broad spectrum of inherited retinal diseases ranging from severe autosomal recessive Leber congenital amaurosis to later onset retinitis pigmentosa. AIPL1 is a photoreceptor-specific co-chaperone that interacts with HSP90 to facilitate the stable assembly of retinal cGMP phosphodiesterase, PDE6. In this report, we establish unequivocal correlations between patient clinical phenotypes and in vitro functional assays of uncharacterized AIPL1 variants. We confirm that missense and nonsense variants in the FKBP-like and tetratricopeptide repeat domains of AIPL1 lead to the loss of both HSP90 interaction and PDE6 activity, confirming these variants cause LCA. In contrast, we report the association of p.G122R with milder forms of retinal degeneration, and show that while p.G122R had no effect on HSP90 binding, the modulation of PDE6 cGMP levels was impaired. The clinical history of these patients together with our functional assays suggest that the p.G122R variant is a rare hypomorphic allele with a later disease onset, amenable to therapeutic intervention. Finally, we report the primate-specific proline-rich domain to be dispensable for both HSP90 interaction and PDE6 activity. We conclude that variants investigated in this domain do not cause disease, with the exception of p.A352_P355del associated with autosomal dominant cone-rod dystrophy.

Indexed as

Adaptor Proteins, Signal TransducingAdolescentAdultAgedAllelesAnimalsCHO CellsCricetulusCyclic Nucleotide Phosphodiesterases, Type 6DNAEpitopesGene FrequencyGenetic VariationHEK293 CellsHeterozygoteHomozygoteAdaptor Proteins, Signal TransducingAIPL1 protein, humanCyclic Nucleotide Phosphodiesterases, Type 6DNAEpitopesHSP90 Heat-Shock Proteins

Identifiers

PMID33067476
PMCPMC7567831
OpenAlexW3092823207

What OpenQuestion holds

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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.