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

To investigate 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 having Usher syndrome (USH) or nonsyndromic retinitis pigmentosa (NSRP) and stratified by the number of truncating USH2A variants (0, 1, or 2). Best-corrected visual acuity, 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%); the mean age was 44.3 ± 12.7 years. Among the 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 the alleles. At least 1 c.2802T>G allele was present in 82 patients (45.1%), including 4 homozygotes. Both USH 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 1 c.2802T>G allele, supporting inclusion of East Asian patients in emerging exon 13-targeted therapies.