Next-generation sequencing--based genetic testing and phenotype correlation in retinitis pigmentosa patients from...

Area of Science:

• Ophthalmology
• Genetics
• Medical Diagnostics

Background:

• Inherited retinal dystrophies (IRD) are a group of genetic disorders causing photoreceptor degeneration.
• Retinitis pigmentosa (RP) is the most common form of IRD, leading to progressive vision loss.
• Genetic testing, particularly panel-based approaches, is crucial for diagnosing RP, identifying causative mutations in a significant percentage of patients.

Purpose of the Study:

• To investigate the efficacy of next-generation sequencing (NGS)-based targeted gene panel testing in diagnosing RP.
• To establish genotype-phenotype correlations in a cohort of RP patients.
• To improve diagnostic accuracy and patient counseling for RP.

Main Methods:

• Retrospective analysis of 107 RP patients undergoing IRD gene panel testing.
• Comprehensive ophthalmic examinations and pedigree documentation.
• DNA extraction, targeted NGS, and co-segregation analysis for mutation confirmation.

Main Results:

• Pathogenic mutations were identified in 72 out of 107 patients.
• The mean age of symptom onset was 14 years, with a mean Best Corrected Visual Acuity (BCVA) of 6/48.
• Specific genotype-phenotype correlations were observed, including chorioretinal atrophy patterns and macular lesions associated with particular gene mutations.

Conclusions:

• NGS-based genetic testing significantly enhances the accuracy of RP diagnosis.
• Establishing genotype-phenotype correlations provides valuable prognostic information and aids in patient counseling.
• This approach supports the development and guidance for emerging gene-based therapies for RP.