Clinical and Molecular Findings in PROM1-Associated Inherited Retinal Dystrophies

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Inherited retinal dystrophies (IRDs) are a group of genetic disorders causing progressive vision loss.
• The PROM1 gene plays a critical role in photoreceptor development and maintenance.
• Existing knowledge on genotype-phenotype correlations in PROM1-associated IRDs is incomplete, hindering precise diagnosis and targeted therapies.

Purpose of the Study:

• To investigate the genotype-phenotype associations in patients with PROM1-associated IRDs.
• To analyze clinical variability and inheritance patterns related to specific PROM1 variants.
• To clarify the distinct clinical behaviors associated with different PROM1 mutations.

Main Methods:

• Retrospective analysis of patients with PROM1-related IRDs.
• Comprehensive ophthalmologic examinations including retinography, fundus autofluorescence, OCT, and electrodiagnostic testing.
• Genetic testing (panels or WES), variant classification (ACMG), and familial segregation analysis.

Main Results:

• All patients carried pathogenic or likely pathogenic PROM1 mutations with both autosomal dominant and recessive inheritance.
• Dominant variants typically caused late-onset cone-rod or macular dystrophy; biallelic variants led to early-onset severe rod-cone dystrophy.
• Truncating N-terminal mutations correlated with earlier onset and greater functional impairment, while phenotypic variability suggested modifier gene or environmental influences.

Conclusions:

• PROM1-associated IRDs exhibit significant genetic and clinical heterogeneity, influenced by inheritance patterns and variant types.
• Comprehensive genotypic and phenotypic characterization is crucial for affected individuals.
• Enhanced understanding of PROM1-related IRD pathways can improve prognosis, guide clinical management, and advance genotype-based therapeutic strategies.