X-linked juvenile retinoschisis: phenotypic and genetic characterization

Abstract

Juvenile X-linked retinoschisis (XLRS, MIM#312700) belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography (SD-OCT) images. The mean central foveal thickness was 569.7 µm. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio (<1.0) in all patients. RS1 (NM_000330.3) gene coding exons Sanger sequencing was performed. RS1 c.599G>T (p.R200L) mutation was detected in one case, showing to be pathogenic in silico analysis. c. (92_97) insC (p.W33fs) mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits.

Keywords: RS1 mutation; X-linked retinoschisis; electroretinogram; optical coherence tomography.

Figure 1. Fundus photography and macular appearance of all patients

At the macula of the first patient dystrophic changes, pigment mottling, marked cystic changes can be seen (A1, B1), for the second patient clear spoke-wheel pattern foveal schisis, cystic edema, star-shaped pigment mottling (A2, B2) could be seen, third patient showed foveal schisis and cystic changes (A3, B3).

Figure 2. SD-OCT scans revealed macular schisis with large intraretinal separation for all patients

The CFT of the first patient RE was 600 µm, LE was 661 µm (A1, B1); second patient CFT of the RE was 570 µm, LE was 777 µm (A2, B2); third patient CFT of the RE was 373 µm, LE was 434 µm (A3, B3).