Why this study matters

Usher syndrome is an inherited condition in which retinitis pigmentosa occurs alongside hearing loss. Changes in the USH2A gene are an important cause of Usher syndrome, but they can also cause non-syndromic retinitis pigmentosa (NSRP)—retinal disease without the hearing-related features that define Usher syndrome. Understanding which USH2A variants occur in different populations, and how they relate to vision over time, is essential for accurate genetic counselling, clinical care, and development of treatments that target specific gene regions.

A 2026 study in the American Journal of Ophthalmology examined 182 Korean people with two disease-causing or likely disease-causing USH2A variants. It provides one of the largest detailed looks at the molecular genetics and age-related retinal findings of USH2A-associated retinitis pigmentosa in a Korean cohort.

A distinct East Asian USH2A variant spectrum

The researchers identified 364 disease-associated USH2A alleles across the 182 participants. The most common variant was c.2802T>G (p.Cys934Trp), which represented 23.6% of all identified alleles. The second most frequent was c.8559-2A>G, representing 12.1%.

Notably, the two USH2A variants often described as European “hotspots”—c.2299delG and c.2276G>T—were not found in this Korean group. This result reinforces an important message for families and clinicians: the genetic landscape of USH2A-related disease is not the same in every population. Genetic testing strategies and research priorities need to account for these population-specific patterns.

Missense variants, which change one amino acid in the protein, made up 53.8% of the disease-associated alleles in the study. Nearly half of all participants—82 of 182 people, or 45.1%—carried at least one c.2802T>G allele. Four participants had two copies of this variant.

Usher syndrome and variant type were linked to more severe retinal findings

The cohort included 56 people with Usher syndrome (30.8%) and 126 with non-syndromic retinitis pigmentosa (69.2%). Participants had a mean age of 44.3 years, and the researchers used age-aware statistical modelling to examine differences in retinal measures over time.

They assessed several clinically meaningful features:

  • Best-corrected visual acuity, a measure of central sharpness of vision;
  • Goldmann visual fields, which measure how much peripheral vision remains;
  • Ellipsoid zone (EZ) band length on optical coherence tomography, an imaging marker that reflects the extent of preserved photoreceptor structure; and
  • Widefield fundus and autofluorescence imaging, which document retinal changes across a broad area.

People with Usher syndrome showed worse age-adjusted patterns of visual acuity, visual field, and EZ band length than those with non-syndromic retinitis pigmentosa. In accessible terms, the group with Usher syndrome had evidence of more severe retinal involvement on these measures as age increased.

The study also examined the number of truncating variants each person carried. Truncating variants are genetic changes expected to interrupt production of the usual full-length protein. Participants were grouped according to whether they had zero, one, or two truncating USH2A variants. A greater burden of truncating variants was associated with worse age-adjusted visual acuity, narrower visual fields, and shorter EZ band length.

These findings do not mean that a single genetic result can precisely predict an individual’s future vision. However, they show that both clinical diagnosis—Usher syndrome versus non-syndromic retinitis pigmentosa—and variant type can help explain differences in disease severity across a large patient group.

Relevance for emerging treatment approaches

The high frequency of c.2802T>G in this Korean cohort has particular relevance for treatment development. The authors note that approximately half of participants carried at least one copy of this variant, supporting the inclusion of East Asian patients in emerging therapies directed at USH2A exon 13.

This is significant because therapies designed around a particular exon or genetic region can only be relevant to people whose variants fall within that target. Studies such as this one help clarify which communities may be represented by, or potentially eligible for, variant-targeted research. They also emphasize why comprehensive genetic testing is a foundational step for individuals and families affected by USH2A-related retinal disease.

Looking ahead

This research expands the evidence that USH2A-associated retinal disease has both shared and population-specific features. For Korean and other East Asian communities, c.2802T>G may be especially important for genetic interpretation and future therapeutic planning. The study also strengthens the link between truncating-variant burden, Usher syndrome diagnosis, and more severe retinal changes.

As genetic studies include more diverse populations and follow patients across longer periods, researchers will be better positioned to refine prognosis, select meaningful clinical trial measures, and ensure that emerging treatments are developed with global patient communities in mind.