Abstract
PURPOSE: The ciliopathies are a broad category of pleiotropic disease with numerous genes involved in pathogenesis. One of the genes implicated in the ciliopathies is WDR19, which can lead to several syndromic diseases that may manifest with a form of retinal degeneration. There is a lack of reporting on the WDR19-mediated retinal phenotype, and therefore warrants more clinical investigation. With retinal degeneration being the most prevalent symptom among the ciliopathies, phenotypic reporting is needed to enhance understanding of pathogenesis. METHODS: Clinical, imaging, and diagnostic records of patients with two variants in the WDR19 gene and a form of retinal degeneration were retrospectively reviewed. Two different individuals analyzed the variants in the studied patients using SnapGene (Version 4.3.11), employing both the canonical NGG PAM and the NGA PAM prime editors. RESULTS: Four patients from three families each carrying biallelic variants the WDR19 gene were reviewed. Two of the six unique variants identified among the patients were novel. Two identical twin patients presented with a recessive Stargardt (STGD)-like phenotype while the other two patients presented with a clinical picture more characteristic of retinitis pigmentosa (RP). Three of four patients had thickened external limiting membrane (ELM) on spectral-domain optical coherence tomography (SD-OCT). Full-field electroretinograms (ffERG) performed on two patients with the STGD-like phenotype showed a cone-rod pattern of degeneration. Quantitative short-wave fundus autofluorescence (qAF) performed on the two STGD-like patients was within the 95th percentile of normal eyes. CONCLUSIONS: WDR19-mediated retinal degeneration is heterogenous in presentation, and in some cases can phenocopy STGD. The foveal sparing phenotype was apparent in three of four patients with relatively preserved visual acuity, which may serve as a retinal prognostic factor in patients with pathogenic variants in WDR19. All six variants evaluated are correctable by prime editing, establishing a foundation for future research in therapeutic development.