Four novel RS1 gene mutations in Polish patients with X-linked juvenile retinoschisis

Abstract

Purpose: To determine the clinical features and to identify mutations in the retinoschisis gene (RS1) in ten patients with X-linked retinoschisis (XLRS).

Methods: Ten male patients from nine Polish families were included in this study. Ophthalmologic examinations, including optical coherence tomography (OCT) and full-field electroretinography (ERG), were performed in all affected boys. The entire coding region encompassing six exons of the RS1 gene was amplified with PCR and directly sequenced in all the patients.

Results: All affected individuals showed typical retinoschisis signs and symptoms, and all appeared to have a mutation in the RS1 gene. Seven different mutations were identified, including two novel missense substitutions: c.176G>C (p.Cys59Ser), c.451T>A (p.Tyr151Asp); one novel nonsense substitution: c.218C>A (p.Ser73*); and one novel frameshift mutation: c.354_355delCA (p.Asp118Glufs*2). We also found two missense substitutions that had been previously described: c.214G>A (p.Glu72Lys) and c.626G>T (p.Arg209Leu) and one known splice site mutation in intron 5: c.522+1G>T (IVS5+1G>T).

Conclusions: This study provides the first molecular genetic characteristics of patients with juvenile retinoschisis from the previously unexplored Polish population. We investigated the molecular background of XLRS in ten boys. The present study reports for the first time four novel mutations, including two missense substitutions, one nonsense substitution, and one frameshift deletion. One of these substitutions and 2-bp deletion created stop codons. Moreover, we described three substitutions that had been previously reported (one is a splicing mutation). Further genetic characterization of Polish patients with XLRS will be helpful in understanding the worldwide spectrum of RS1 mutations. Despite the mutation heterogeneity found in a small group of our patients, they presented a relatively uniform clinical picture. Identifying the causative mutation is helpful in confirming diagnosis and counseling, but cannot provide prognostic data.

Figure 1

Pedigrees of families with X-linked juvenile retinoschisis with positive family history. Black squares represent affected boys. Circles with black dots denote obligate carriers. Arrows point to probands. Slashed circles and squares are deceased family members. Blue digits indicate the patients’ numbers.

Figure 2

OCT and ERG results of patient 2. A: OCT image of the right eye showing foveal cystic retinoschisis. B: OCT image of the left eye showing foveal atrophy. C, D: Standard scotopic response of full-field ERG of the right and left eye showing decreased b-wave amplitude

Figure 3

Chromatogram showing the c.218C>A (p.Ser73*) mutation. The upper part of the picture shows the wild-type nucleotide sequence and wild-type protein, while the lower one shows the nucleotide sequence with c.218C>A mutation and truncated protein.