Genotype and phenotype characteristics of X-linked retinoschisis: the first report of a Turkish population

Background X-linked retinoschisis is an inherited retinal disease caused by mutations in the RS1 gene; however, a genotype-phenotype correlation regarding the mutation type or location within the RS1 gene and clinical characteristics of the patients has not been established yet. This is the first report documenting the genotypes and ophthalmological findings in a Turkish population with confirmed RS1 mutations. Materials and Methods Fifty eyes of 25 male patients were included in the study. RS1 mutation analysis was performed by DNA sequencing. Retrospective analysis of ocular examinations and SD-OCT scans were applied. Results The major mutation was c.422 G > A (p.Arg141His, exon 5) affecting 14 patients (56%) and c.531 T > G was the only non-sense mutation out of 7 pathogenic variants. At presentation; the mean age was 24.6 +/- 16.2 (4-72) years, mean visual acuity (VA) was 0.61 +/- 0.32 (logMAR, 0.10-1.30). Forty-six (92%) eyes had macular, 16 eyes (32%) had peripheral retinoschisis. None of the eyes had macular scar, whereas 7 eyes (14%) had macular atrophy. The most frequent location of schisis was inner nuclear layer (37.5%). The eyes with disruption of ellipsoid zone (EZ) or external limiting membrane (ELM) had worse VA (for EZ, 0.65 +/- 0.25 versus 0.45 +/- 0.34, logMAR, 31 versus 17 eyes, p = .013; for ELM, 0.66 +/- 0.27 versus 0.45 +/- 0.31, logMAR, 30 versus 18 eyes, p = .008). Conclusions Seven different pathogenic variants in the RS1 gene were identified; with c.422 G > A (p.Arg141His) as the most frequent variant and c.531 T > G as only non-sense mutation. Having EZ or ELM disruption were the significant factors affecting VA.