Expanding Genetic and Clinical Spectra of Inherited Retinal Dystrophies: Identification of Three Novel PRPH2 Variants

TL;DR

This study identifies three new genetic variants in the PRPH2 gene linked to inherited retinal diseases, improving diagnosis and understanding of these conditions.

Contribution

The study reports three novel PRPH2 variants and emphasizes integrating genetic and clinical data for better diagnosis of IRDs.

Findings

Three novel PRPH2 variants (c.653C>G, c.700T>C, c.121del) were identified in patients with inherited retinal dystrophies.

Combining genetic, clinical, and instrumental data improves diagnostic accuracy and genotype–phenotype correlations.

Seven previously reported PRPH2 variants were also documented in the study.

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.

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