Vestn Oftalmol. 2026;142(1):70-78. doi: 10.17116/oftalma202614201170.
ABSTRACT
PURPOSE: The primary objective of the study was to investigate and describe the molecular genetic characteristics of patients with inherited retinal dystrophies (IRDs) presenting with phenotypes of Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP), taking into account clinical polymorphism.
MATERIAL AND METHODS: This noninterventional cohort study was conducted in Russia by collecting retrospective data from patients with LCA and RP phenotypes and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes, entered into the registry between July 20, 2022 and March 3, 2025. Eligible participants were entered into the IRD database, followed by a two-stage genetic diagnostic algorithm to confirm the presence of biallelic mutations in RPE65 or RLBP1. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.
RESULTS: The study cohort included 2425 patients with IRDs from 83 regions of the Russian Federation. The mean age was 23.22±16.74 years, with predominance of pediatric patients (51.34%) and males (52.99%).
Genetic testing was performed in two stages. At the first stage, mutations in RPE65 and/or RLBP1 were identified in 84 (3.52%) of 2388 examined patients. The second stage involving direct Sanger sequencing was conducted in 48 (2.01%) patients, it confirmed biallelic mutations in RPE65 in 1.68% and in RLBP1 in 0.04% of cases. In one case, mutations in both genes were verified. Among RPE65 variants, 61 mutations were identified, including frequent pathogenic variants (c.304G>T, c.272G>A, c.370C>T); seven variants were detected in the RLBP1 gene.
The frequency of biallelic RPE65 mutations in the subgroup with LCA/RP phenotype was 1.68%, and 1.65% in the overall IRD cohort, which is consistent with published data from European populations.
CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia” allowed characterization of the key molecular genetic features of a representative sample of patients with IRDs.
PMID:41847810 | DOI:10.17116/oftalma202614201170
