Clinical characterization and molecular analysis of X-linked juvenile retinoschisis in a northern Chinese cohort

This study aims to explore the clinical features and genetic findings associated with X-linked juvenile retinoschisis (XLRS) in affected patients.

This study included 16 patients with XLRS from 13 unrelated families between 2016 and 2024. Genomic DNA from peripheral blood leukocytes of the probands were subjected to whole-exome sequencing or direct sequence. Comprehensive analyses of molecular genetic profiles and detailed ophthalmic evaluations were performed.

We identified 12 retinoschisin 1 (RS1) variants, and five of them were novel. Missense variants (7/9, 75%) in the discoidin domain were the most common mutations. All 16 patients aged 4-45 years old were males, and the mean visual acuity was 0.58 ± 0.49 (Log MAR). The funduscopic observations were consistent with typical XLRS presentations. Notably, distinctive clustered pigmentation exhibited 75% penetrance (3/4 cases) in individuals harboring the novel Q43* mutation. Optical coherence tomography revealed macular schisis in 27 eyes (87.1%), peripheral schisis in six eyes (19.35%), and retinal atrophic changes in five eyes (16.13%). Schisis predominantly affected the inner nuclear layer (27/31, 87.10%). Additionally, other less common abnormalities included asymmetric schisis in patients with the R182C variant, presenting with schisis in one eye and a relatively normal fellow eye. Furthermore, two individuals with the Q43* nonsense mutation exhibited mild electroretinogram abnormalities with a preserved b-to-a amplitude ratio. Given these findings, larger multicenter studies are warranted to validate the observed associations.

This study comprehensively analyzed the genetic and clinical features of XLRS in a northern Chinese cohort. Five novel variants were identified, expanding the known mutational spectrum and enriching the clinical manifestation. Distinct pigment clusters (Q43*) and asymmetric schisis (R182C) appeared consistently within our limited cohort carrying specific mutations, which may potentially facilitate the diagnosis of XLRS.