A novel deletion mutation in RS1 gene caused X-linked juvenile retinoschisis in a Chinese family

Abstract

Purpose: X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. This study aimed to identify the underlying genetic defect in a Chinese family with XLRS.

Methods: The proband underwent complete ophthalmic examinations, including fundus examination, fundus autofluorescence, and optical coherence tomography. DNA extracted from proband and his younger brother was screened for mutations in RS1 gene. The detected RS1 mutation was tested in all available family members and 200 healthy controls.

Results: Reduced visual acuity, spoke-wheel pattern at the fovea, and split retina were observed in the proband. A novel frameshift mutation c.206-207delTG in the RS1 gene, leading to a truncated protein (p.L69fs16X), was identified in the proband and his younger brother. This mutation was not found in any unaffected member or in the healthy controls. The mother of the proband was hemizygous for this mutant allele.

Conclusions: We identified a novel causative mutation of RS1 in a Chinese family with XLRS. This finding expands the mutation spectrum of RS1 and provides evidence for a phenotype-genotype study in XLRS.

Figure 1

Pedigree of X-linked juvenile retinoschisis Chinese family. Black symbols indicate affected individuals and white symbols indicate unaffected individuals. The arrow indicates the proband.

Figure 2

Eye examination of the proband (III1). R: right eye; L: left eye. (a) Fundus photography, (b) fundus autofluorescence, and (c) optical coherence tomography.

Figure 3

Genetic characterization of the RS family. (a) Sequencing result of the normal individuals. (b) Sequencing result of the proband and his younger brother showing the two-base deletion (c.206-207delTG) in RS1. (c) Sequencing result of the proband's mother showing heterozygous deletion (c.206-207delTG) in RS1. (d) Relative position of the mutation in RS1. (e) Evolutionary conservation of amino acids: the box shows loss of the conserved leucine residue and truncation of protein in the proband and in his younger brother.