Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis

Purpose: X-linked retinoschisis (XLRS) is an early-onset retinal degenerative disorder caused by mutations in the RS1 gene. The objective of this study was to describe the clinical and genetic findings in 90 unrelated Chinese patients with XLRS. Methods: All patients underwent clinical examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, and spectral domain-optical coherence tomography (SD-OCT). A combination of molecular screening methods, including Sanger-DNA sequencing of RS1 and targeted next-generation sequencing (TES), were used to detect mutations. In silico programs were used to analyze the pathogenicity of all the variants. Long-range PCR with subsequent DNA sequencing was employed to find the breakpoints of large deletions. Results: The 90 probands (mean age 17.29 +/- 12.94 years; 3-52 years) showed a variety of clinical phenotypes, and their average best correct visual acuity was 0.81 +/- 0.48 (logarithm of the minimal angle of resolution, 0-3). Of the 175 eyes analyzed, 140 (80%) had macular retinoschisis, 84 (48%) had peripheral retinoschisis, 28 (16%) had macular atrophy, and five (3%) had a normal macular structure. We identified 68 mutations in this cohort of patients, including 15 novel mutations. Most mutations (65%) were missense; the remaining null mutations included nonsense, splicing effect, frame-shift indel, and large genomic DNA deletions. The 62 patients with missense mutations seemed to have relatively milder visual defects than the 28 patients with null mutations. Conclusions: Patients with RS1 mutations present profound phenotypic variability and show no clear genotype-phenotype correlations. Patients with null mutations tend to have more severe XLRS-related visual defects.