Background: Little is known about genotype–phenotype correlations of RP1-associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of RP1 variants and provide a detailed description of the clinical findings in Japanese patients. Methods: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an Alu element insertion (c.4052_4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous RP1 variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic RP1 variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD. Results: We identified 18 pathogenic RP1 variants, including seven novel variants. Interestingly, the Alu element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients. Conclusions: Our results suggest a genotype–phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the Alu element insertion was the most major variant in Japanese patients with RP1-associated retinal dystrophies.

Background/Objectives: To characterize the early clinical manifestations and treatment outcomes of Japanese patients with Norrie disease. Retrospective multicenter observational case series with a systematic literature review. Methods: Fourteen infants with genetically confirmed Norrie disease were retrospectively reviewed. Clinical findings, disease stage, interocular asymmetry, treatment, and visual outcomes were evaluated using a modified staging system based on familial exudative vitreoretinopathy (FEVR) and the International Classification of Retinopathy of Prematurity. A systematic review of previously reported Japanese cases was performed to assess disease severity at initial diagnosis. Results: Twenty-eight eyes of 14 patients were included. The median age at the initial examination was 2.5 months. Twenty-three eyes (82%) had stage 5 retinal detachment, whereas only five eyes (18%) had stage 2 or 4 disease. Interocular asymmetry was uncommon. Twenty-one eyes (75%) underwent laser photocoagulation and/or surgery. Visual outcomes were poor; at the most recent follow-up, all but two stage 4 eyes treated with laser photocoagulation had no light perception. Combined analysis of our cohort and the literature review identified 29 Japanese patients from 19 families and demonstrated that most already had advanced bilateral retinal detachment within the first two months of life. Conclusions: Norrie disease typically presents with advanced bilateral retinal detachment during early infancy, leaving limited opportunities for effective intervention. Early recognition and genetic diagnosis are therefore essential.