Minigene Splice Assays Allow Pathogenicity Reclassification of RPE65 Variants of Uncertain Significance
Following the 2023 established ClinGen specific ACMG guidelines for <i>RPE65</i> (Criteria Specification Registry), evidence from splice assays enabled reclassification of seven <i>RPE65</i> variants from VUS to pathogenic through an assigned PVS1-very-strong criterium, as less than 5% of wild-type transcript was present. These findings contribute to the interpretation of variants observed in patients, which will in turn dictate their eligibility for gene therapy.
Authors
- Zelia Corradi (ORCID: https://orcid.org/0000-0002-2934-497X)
- Daan M. Panneman (ORCID: https://orcid.org/0000-0002-4384-505X)
- Erica G. M. Boonen (ORCID: https://orcid.org/0000-0003-1509-3150)
- Susanne Roosing (ORCID: https://orcid.org/0000-0001-9038-0067)
- Frans P.M. Cremers (ORCID: https://orcid.org/0000-0002-4954-5592)
Institutions
- Radboud University Nijmegen (NL)
- University Medical Center (US)
- Radboud University Medical Center (NL)
- Rotterdam Eye Hospital (NL)
Publication Details
- Journal
- Genes
- Published
- 2025-08-28
- DOI
- https://doi.org/10.3390/genes16091022
- Citations
- 1
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Radboud Universitair Medisch Centrum
- Stichting Blinden-Penning
- Stichting Blindenhulp
- Stichting tot Verbetering van het Lot der Blinden