Clinical Exome-Based Redefinition and Reclassification of Retinitis Pigmentosa

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Inherited retinal diseases, including retinitis pigmentosa (RP), have low prevalence, leading to limited data on RP-related gene distribution in Korean populations.
• Previous reports on Korean patients with RP are scarce, necessitating further investigation into genetic causes.

Purpose of the Study:

• To determine the mutation spectrum and allele frequency of RP-related genes in a Korean cohort.
• To analyze the final diagnoses in Korean patients clinically diagnosed with RP based on genetic findings.

Main Methods:

• Whole-exome sequencing (WES) was performed on 100 unrelated Korean patients clinically diagnosed with RP.
• Variant pathogenicity was assessed using American College of Medical Genetics and Genomics guidelines, in-silico tools, clinical phenotypes, and inheritance patterns.

Main Results:

• Causative genes were identified in 60% (60/100) of patients.
• USH2A (23.3%), EYS (21.7%), and RP1 (10.0%) were the most frequent causative genes.
• Genetic testing led to diagnostic reclassification in 15% (9/60) of cases, including choroideremia (CHM), Leber congenital amaurosis (RDH12, RPGRIP1), Bietti's crystalline dystrophy (CYP4V2), and cone-rod dystrophy (ABCA4).

Conclusions:

• This study provides the first comprehensive report on the mutational spectrum of RP in a Korean cohort.
• The findings offer valuable insights into gene frequencies, their association with symptom onset, and their role in various inherited retinal degenerations.
• Genetic testing is crucial for accurate diagnosis and understanding the genetic landscape of RP in Korea.