Genotype-Phenotype Correlations in 83 Korean X-linked Retinoschisis Patients: Impact of Retinoschisin 1 Secretion Profiles on Clinical Phenotypes

Ophthalmol Retina. 2024 Sep 16:S2468-6530(24)00431-7. doi: 10.1016/j.oret.2024.09.007. Online ahead of print.

Abstract

Purpose: To assess the correlation between genotype and phenotype severity in X-linked juvenile retinoschisis (XLRS) by examining clinical and genetic features of a cohort of Korean XLRS patients.

Design: Retrospective, observational study.

Participants: Data from 83 consecutive male patients with molecularly confirmed XLRS were collected retrospectively.

Methods: Clinical evaluation included best-corrected visual acuity (BCVA), fundus photography, spectral domain OCT (SD-OCT), and full-field electroretinography (ERG).

Main outcome measures: The phenotypic characteristics of a cohort of pediatric Korean patients with XLRS, based on mutation types (truncating vs. missense) and secretory profile (secretion vs. nonsecretion), were assessed.

Results: A total of 166 eyes of 83 patients were included. The mean age at diagnosis was 6.1 ± 8.8 years (range, 0.5-20.7 years), with a mean follow-up time of 9.2 ± 7.0 years (range, 0.6-24.3 years). The BCVA at first and last examination ranged from light perception to 0.1 logarithm of the minimum angle of resolution (mean ± standard deviation, 0.75 ± 0.59 and 0.82 ± 0.65, respectively). No significant differences were observed between the truncating (0.71 ± 0.51 and 0.75 ± 0.44) and missense (0.77 ± 0.59 and 0.84 ± 0.66) variants (P = 0.678 and 0.551). Clinical parameters from fundus photography, SD-OCT, and ERG showed no differences. However, BCVA was better for the secretion group (0.51 ± 0.24 and 0.61 ± 0.30) than for the nonsecretion group (0.65 ± 0.71 and 0.87 ± 0.81), with a significant difference in the last BCVA (P = 0.021). OCT revealed a higher frequency of ellipsoid zone disruption in the nonsecretion group (P = 0.030), with no significant differences in other parameters.

Conclusions: The secretion profile of Retinoschisin 1 (RS1) could influence the severity of XLRS phenotypes. Patients with RS1-secreted mutants, particularly with intact octamerization, exhibit more homogeneous phenotypes and better visual acuity than the RS1-nonsecreted group. This data provide insights for studying genotype and phenotype correlations in both clinical and research fields.

Financial disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Genotype; Mutation spectrum; Phenotype; X-linked retinoschisis.