Abstract
Background/Objectives: Pathogenic variants in the PRPH2 gene are implicated in a wide spectrum of Inherited Retinal Dystrophies (IRDs), which show significant phenotypic heterogeneity. This study combines genomic, clinical, and instrumental data, including BCVA, OCT, ERG, and visual field testing, using a multimodal approach to identify known and novel PRPH2 variants, with the aim of refine genotype-phenotype correlations and improving the diagnosis of IRDs. Methods: A total of 830 Italian subjects diagnosed with IRDs by the multimodal clinical approach underwent WES on the Illumina(®) Next-Seq 550 system. Genetic variants were evaluated by considering type, frequency, and pathogenicity using dedicated databases and bioinformatics tools. Results: WES analysis led to the identification of three novel PRPH2 variants (c.653C>G, c.700T>C, c.121del) and seven previously reported variants (c.424C>T, c.458A>G, c.461_463del, c.493T>C, c.499G>A, c.612C>G, c.734dup) documented in public databases and the scientific literature. Conclusions: Our data confirm the wide spectrum of IRDs associated with PRPH2 genetic variants and highlight the importance of integrating genetic, clinical, and instrumental data. This strategy enhances diagnostic accuracy and strengthens genotype-phenotype correlations, ultimately improving clinical decision-making and personalized patient management.