PRPH2-Associated Retinopathy: Novel Variants and Genotype-Phenotype Correlations

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Peripherin-2 (PRPH2) gene variants are linked to various autosomal-dominant inherited retinal diseases (IRDs), including pattern dystrophy and cone-rod degeneration.
• Understanding the genotype-phenotype correlations in PRPH2-associated IRDs is crucial for diagnosis and management.

Purpose of the Study:

• To perform detailed clinical and molecular characterization of patients with PRPH2-associated IRDs.
• To expand the known spectrum of PRPH2 mutations.
• To establish novel genotype-phenotype correlations in peripherinopathies.

Main Methods:

• Retrospective case series of 19 patients with molecularly confirmed PRPH2 variants.
• Ophthalmic examinations including OCT, fundus autofluorescence, and ultra-widefield imaging.
• Genomic analysis using next-generation sequencing.

Main Results:

• 19 patients with IRDs and PRPH2 variants were identified; 7 variants were novel.
• Disease onset typically in the 30s-40s, with a median follow-up of 4 years.
• Missense variants in the D2 loop correlated with cone-rod dystrophies, while loss-of-function alleles were associated with pattern dystrophies.

Conclusions:

• This study expands the PRPH2 mutational spectrum with 7 newly identified variants.
• Distinct PRPH2 variant types (missense vs. loss-of-function) correlate with specific IRD phenotypes and visual outcomes.
• Further research is needed to elucidate pathogenetic mechanisms and inform gene therapy development.