Understanding variable disease severity in X-linked retinoschisis: Does RS1 secretory mechanism determine disease severity?

PloS One
Dhandayuthapani SudhaJayamuruga Pandian Arunachalam

Abstract

X-linked retinoschisis (XLRS) is a retinal degenerative disorder caused by mutations in RS1 gene leading to splitting of retinal layers (schisis) which impairs visual signal processing. Retinoschisin (RS1) is an adhesive protein which is secreted predominantly by the photoreceptors and bipolar cells as a double-octameric complex. In general, XLRS patients show wide clinical heterogeneity, presenting practical challenges in disease management. Though researchers have attempted various approaches to offer an explanation for clinical heterogeneity, the molecular basis has not been understood yet. Therefore, this study aims at establishing a link between the phenotype and genotype based on the molecular mechanism exerted by the mutations. Twenty seven XLRS patients were enrolled, of which seven harboured novel mutations. The mutant constructs were genetically engineered and their secretion profiles were studied by in vitro cell culture experiments. Based on the secretory profile, the patients were categorized as either secreted or non-secreted group. Various clinical parameters such as visual acuity, location of schisis, foveal thickness and ERG parameters were compared between the two groups and control. Although the two groups sh...Continue Reading

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Citations

Aug 15, 2021·Progress in Retinal and Eye Research·Camasamudram VijayasarathyPaul A Sieving

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Methods Mentioned

BETA
PCR
transfection
immunoprecipitation assay
electrophoresis
genotyping

Software Mentioned

pymol
Schrödinger
PolyPhen
Desmond
Prime
SIFT
Ensembl
PDBsum server
PHYRE
Statistical Package for the Social Sciences ( SPSS )

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