Genotype-Phenotype Correlations in -Associated Retinal Dystrophies: A Multi-Center Cohort Study in JAPAN.

Background: Little is known about genotype-phenotype correlations of -associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of 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 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 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 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 variants, including seven novel variants. Interestingly, the 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 element insertion was the most major variant in Japanese patients with -associated retinal dystrophies.