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Jun Kong, Wei Sun, Tingyu Yan, Xinxin Zhang, Na Yang, Neil Bressler; Identification of Two Potentially Novel Mutations in X-linked Juvenile Retinoschisis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4511.
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© ARVO (1962-2015); The Authors (2016-present)
X-linked retinoschisis (XLRS), also known as X-linked juvenile retinoschisis, is one of the leading causes of macular degeneration in male children. Here, we report two potentially novel mutations in two Chinese pedigrees with XLRS and attempt to link the phenotypes with corresponding genotypes.
A total of fourteen participants in these two XLRS pedigrees were analyzed. Standard ophthalmic examinations were performed, including visual acuity, fundus examination and optical coherence tomography (OCT). Gene sequencing was conducted for all the family members, and the mutation sites were located. Protein construction prediction was performed. According to the results, we constructed vectors and built the huh7 cell line to express RS1 (Retinoschisin 1) with FLAG tag in wild type and mutant. Western blotting and nondenaturing gel electrophoresis were used to analyze the structure and expression of mutant RS1 protein.
The clinical results illustrated that severity and width of the retinoschisis OCT of the propositus from family 1 was more severe [NB1] than those of the propositus in family 2. By direct sequencing of the RS1 gene, one missense mutation (c.599G>C) in exon 6 of RS1 gene was identified in family 1. Another frameshift mutation (c.549delC) in exon6 of RS1 gene was identified in family 2. To our knowledge, the two mutants have not been reported previously following a review of Human Gene Mutation Database. The results of protein construction prediction identified that the gene mutation in family 1 did not change the conformation of RS1 protein, while the gene mutation in family 2 caused depolymerization of the structure of the octomer which may influence retinoschisin’s function.
We identified two potentially novel RS1 mutations in two Chinese pedigrees and evaluated the spatial conformation changes of the RS protein induced by the mutations. This finding expands the RS1 mutation spectrum and may help to further understand the molecular pathogenesis of XLRS and to predict the level of severity of XLRS by identifying the mutation sites.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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