R213W mutation in the retinoschisis 1 gene causes X-linked juvenile retinoschisis in a large Chinese family

Abstract

Purpose: We identified a large Chinese family with X-linked juvenile retinoschisis. The purpose of this study was to report the clinical findings of the family and to identify the genetic mutation by screening the retinoschisis 1 (RS1) gene.

Methods: Family history was collected and all family members underwent routine ophthalmic examination. Venous blood was collected from family members and genomic DNA was extracted. The exons of RS1 were screened by PCR followed by direct sequencing and/or restriction enzyme digestion.

Results: The pedigree of interest was a four-generation family with 52 family members, including seven affected individuals. The proband was a 5-year-old boy showing highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both eyes. Vitrectomy was performed in the left eye of the proband. Five affected males showed large peripheral retinoschisis in both eyes, either involving the macula or combined with foveal stellate cystic change. One of the affected family members showed only a foveal stellate cystic change in both eyes without periphery retinoschisis. Visual acuity of affected individuals ranged from hand motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected individuals, predicting an amino acid substitution of arginine to tryptophan at codon 213.

Conclusions: Our data show that the R213W mutation in RS1 causes various severities of retinoschisis in a large Chinese family, providing further evidence for X-linked juvenile retinoschisis phenotypic variability.

Figure 1

Pedigree of the Chinese family with X-linked juvenile retinoschisis. Squares represent males, and circles represent females. Solid symbols indicate affected subjects with X-linked juvenile retinoschisis (XLRS). Unfilled symbols represent unaffected family members. A diagonal line indicates a deceased family member. The arrow indicates the proband (III-14).

Figure 2

Photographs for the proband (III-14) of the family with X-linked juvenile retinoschisis. A: Fundus photograph of the right eye. B: Fundus photograph of the left eye. C: Slit-lamp photograph showing a membrane with blood vessels behind the lens. D: Ultrasonography of the right eye and left eye. E: Fundus photograph of the left eye after vitrectomy.

Figure 3

Fundus photographs for the elder brother (III-13) of the proband. Panel A describes the right eye showing a foveal stellate cystic change and a peripheral retinoschisis in the upper temporal retina. Panel B describes the left eye showing peripheral retinoschisis involving the macula.

Figure 4

Mutation screening of the retinoschisis 1 gene for the proband, his elder brother, and their parents in the Chinese family with X-linked juvenile retinoschisis. A missense mutation of c.637C>T (R213W) in exon 6 of the retinoschisis 1 (RS1) gene was identified for the proband (III-14) and his brother (III-13). The mother (II-6) was heterozygous for the mutation, and the father (II-7) was normal.

Figure 5

Representative 2% agarose gel of the restriction enzyme digestion analysis using MspI. The enzyme cut the PCR products into two fragments in unaffected males (I-4, II-20) and the normal female (II-4) but could not cut the products in affected males (II-10, III-22, III-23). Female carriers (I-3, II-6, II-19) exhibit a heterozygous status.