USH2A-Associated Retinitis Pigmentosa in Koreans: Molecular Genetics and Clinical Characteristics

To describe the molecular genetic spectrum and age-related clinical features of USH2A-associated retinitis pigmentosa in Korean patients.

Retrospective cohort study.

A total of 182 Korean patients with biallelic pathogenic or likely pathogenic USH2A variants were included. Patients were classified as Usher syndrome (USH) or non-syndromic retinitis pigmentosa (NSRP), and stratified by the number of truncating USH2A variants (0, 1, or 2). Best-corrected visual acuity (BCVA), Goldmann visual field, ellipsoid zone (EZ) band length on optical coherence tomography, and ultra-widefield fundus and autofluorescence imaging were assessed. Age-related changes were modeled using restricted cubic splines with generalized estimating equations.

The cohort comprised 56 patients with USH (30.8%) and 126 with NSRP (69.2%); mean age was 44.3 ± 12.7 years. Among 364 pathogenic or likely pathogenic alleles, c.2802T>G (p.Cys934Trp) was the most common (23.6%), followed by c.8559-2A>G (12.1%). The European hotspots c.2299delG and c.2276G>T were not identified. Missense variants accounted for 53.8% of alleles. At least one c.2802T>G allele was present in 82 patients (45.1%), including 4 homozygotes. Both Usher syndrome and an increasing truncating variant burden were associated with worse age-adjusted patterns of visual acuity, visual field, and EZ band length.

USH2A-associated retinitis pigmentosa in Korean patients follows an East Asian variant spectrum that is distinct from European populations. Approximately half of patients carried at least one c.2802T>G allele, supporting inclusion of East Asian patients in emerging exon 13-targeted therapies.