Purpose Biallelic variants in the retinal pigment epithelium–specific 65-kDa protein (RPE65) gene are linked to several inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). This study screened patients from a tertiary center in Brazil with IRDs for RPE65 variants to characterize the associated phenotypes. Methods LCA, EOSRD, and RP diagnoses were based on predefined clinical criteria. Patients underwent comprehensive clinical evaluations and retinal imaging. Genomic DNA was analyzed using a next-generation sequencing panel for IRDs, covering 238 genes. Results RPE65 variants were identified in seven of the 68 patients screened. Of these, three were homozygous, and four were compound heterozygous for the identified mutant alleles. A total of six variants were detected, of which one was novel. The p.Leu341Ser (c.1022TC) mutation was the most prevalent, being found in four of seven patients. Visual loss onset ranged from birth to the third decade of life. A consistent clinical feature observed in all patients was some degree of pigmentary change upon peripheral retinal examination. Conclusions RPE65 variants were found in 10.3% of cases in this series, associated with LCA, EOSRD, and RP. These variants were consistently linked with pigmentary changes in the peripheral retina and exhibited variable manifestations regarding arteriolar attenuation, disc pallor, and macular appearance. In this series, the prevalence of the p.Leu341Ser (c.1022TC) mutation was 57%.
Cenachi et al. (2025) studied this question.