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K. A. Drenser, N. Sund, W. Dailey, M. T. Trese, A. Capone, Jr.; Congenital X-Linked Retinoschisis: Structural and Genetic Evaluation Using a New Classification System. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1669. doi: https://doi.org/.
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The purpose of this study is to better understand Congenital X-linked Retinoschisis (CXLRS) using a new classification system, genetic evaluation of the RS1 gene, and analysis of the intraretinal schisis fluid cavity.
Twenty-two patients with CXLRS underwent ophthalmoscopic examination, OCT analysis, and genetic analsis of the RS1 gene. Patients were classified as Type 1 (foveal schisis), Type 2 (foveal/lamellar schisis), Type 3 (foveal/lamellar/bullous), or Type 4 (foveal/bullous) based on the appearance of the retina and the OCT findings. Genomic DNA was purified from each patient’s blood and direct sequencing with a Beckman CEQ 8000 DNA detection system was used to find the location and type of RS1 mutation. The schisis fluid from patients with Type 3 or 4 CXLRS was analyzed by SDS polyacrylamide electrophoresis. Western blots with anti-retinoschisin polyclonal antibody were also performed on vitreous and schisis fluid samples.
All RS1 mutations were localized to the discoidin domain of RS1. Twelve patients have lamellar schisis (1 Type 2; 11 Type 3). Eight patients without lamellar schisis (6 Type 1; 2 Type 4) have mutations at 2 loci (c214; c305). Two patients did not have mutations in the coding region of RS1. All schisis fluid samples contained high levels of cystatin C and Tenacin-C. Retinoschisin in a multimeric form was present in the schisis fluid samples and was secreted and identified in the vitreous.
There are three possible mechanisms of interference caused by mutations affecting retinoschisin (RS1); those that interfere with; secretion, oligermerization, or function. Western blot analysis indicates that retinoschisin was secreted from the cells and able to form multimeric complexes, consistent with the finding that none of the mutations affected the leader sequence or a cysteine residue. The presence of cystatin C and Tenascin-C in the schisis cavity fluid may implicates a role for inflammation in the formation of schisis cavities and may represent chronic phase reactants to structural damage. The lack of lamellar schisis in patients with with mutations affecting bases 214 and 305 suggests a genotype:phenotype correlation which has previously not been identified. Classification based on OCT findings in addition to clinical examination suggests that lamellar schisis is present in the majority of patients and may correlate with RS1 mutations. Continued evaluation of patients with CXLRS will be needed to confirm these preliminary findings.
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