Phenotypic and Genotypic Characterization of RP1L1-Associated Retinopathy

Pathogenic variants in RP1L1 are associated with autosomal dominant occult macular dystrophy (OMD) and autosomal recessive retinitis pigmentosa (RP). In this study, we investigated the phenotypic and genotypic landscape of RP1L1-associated retinopathy in an ethnically heterogeneous cohort.

This multicenter cohort study retrospectively collected the following data: best-corrected visual acuity (BCVA), color fundus photograph (CFP), optical coherence tomography (OCT), short-wavelength fundus autofluorescence (SW-AF), and full-field electroretinography (ffERG). Patients were classified based on their clinical phenotype in OMD or RP. Atypical cases were analyzed separately and reappraised according to their clinical and genetic findings.

This study included 20 patients (40 eyes) from 19 families: 12 (60%) with OMD, 4 (20%) with RP, and 4 (20%) atypical cases (3 "non-occult" macular dystrophy, 1 rod-cone dystrophy with vitelliform maculopathy). Autosomal dominant OMD was the most common phenotype, with one autosomal recessive OMD case identified. Autosomal recessive RP had the latest onset, best visual acuity, and highest refractive error. OMD BCVA declined by ∼0.5 lines/year over a median follow-up of 3.2 years.

Mutations in RP1L1 cause a spectrum of diseases, including autosomal dominant OMD, autosomal recessive OMD, and autosomal recessive rod-cone dystrophies, occasionally presenting with pseudovitelliform maculopathy.