Characterisation and prevalence of inherited retinal diseases in the Finnish population reveals enrichment of population-specific phenotypes and causative variants

Abstract

<div><p><strong>Aims</strong> This study aims to assess clinical and genetic characteristics as well as the prevalence of inherited retinal dystrophies (IRD) and their subphenotypes in the Finnish founder population.</p></div><div><p><strong>Methods</strong> A retrospective analysis of clinical and genetic data from Northern Finnish patients diagnosed with IRD between 1996 and 2023 at Oulu University Hospital, Finland, was conducted.</p></div><div><p><strong>Results</strong> The cohort comprised 582 patients with IRD, categorised into 16 different subphenotypes. Pathogenic or likely pathogenic variants explaining IRD were identified in 36% (n=210/582) of all patients and 80% (n=210/261) of genetically tested patients with IRD. Diagnostic yields varied between different IRD subphenotypes. The genetic aetiology was most commonly confirmed in X-linked retinoschisis, severe early childhood-onset retinal dystrophy, congenital stationary night blindness and choroideremia. The lowest rates of causative variant identification were observed in cone or cone-rod dystrophy and macular dystrophy. In total, 70 pathogenic or likely pathogenic variants were identified across 39 different genes; variants in the <em>FZD4</em> and <em>RPGR</em> genes were the most prevalent. Over half of the variants were enriched in the Finnish population. The estimated total prevalence of IRDs in Northern Finland was 69.8/100 000 (1:1432). The prevalence of the most common subphenotypes was as follows: retinitis pigmentosa, 25.3/100 000; X-linked retinoschisis, 10.7/100 000; Usher syndrome, 8.9/100 000; choroideremia, 7/100 000 and cone or cone-rod dystrophy, 6/100 000.</p></div><p><strong>Conclusion</strong> The Northern Finnish population exhibits an enrichment of population-specific IRD-associated variants, resulting in a high overall prevalence of IRDs and an increased prevalence of selected retinal subphenotypes, such as retinoschisis, choroideremia and Usher syndrome types 3 and 1<br></p>