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Hiroyuki Kondo, Akihiko Tawara, Eiichi Uchio, Kenshi Hayashi, Tomoko Tahira; Search For SOX17 Gene Mutations In Patients With Familial Exudative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):61.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in genes coding for the components of Norrin/β-catenin signaling are known to cause familial exudative vitreoretinopathy (FEVR). The endothelial marker gene, SOX17 has been recently found to be upregulated by Norrin/β-catenin signaling (Ye et al., Cell 2009). The purpose of this study was to search for possible mutations of SOX17 in patients with FEVR to determine whether this gene is responsible for this disease.
Fifty-five probands (25 familial and 30 simplex) of FEVR, who have no known FEVR mutations in the FZD4, LRP5, TSPAN12, and NDP genes were studied. Direct sequencing following polymerase chain reaction of coding exons of SOX17 was performed.
A homozygous G26R change (c.76G>A) of SOX17 was found in a six-year-old boy who had unilateral leukocoria due to a retinal detachment since infancy. No history of FEVR was found for this family, and the G26R change was not found in the mother and a maternal half-sibling, both of whom had no retinal abnormalities. Because of the lack of segregation, a multiplex ligation-dependent probe amplification and microsatellite genotyping close to SOX17 were performed, and no exon deletion or false maternity was detected for the proband. Codon 26 is highly conserved among vertebrates, and is located within the conserved N-terminal region. This sequence change was not found in 380 chromosomes from 190 healthy volunteers. Computational analysis using programs of function prediction (PolyPhen, PMUT, and SIFT) indicated pathogenic character of the G26R mutation.
A homozygous SOX17 gene mutation was associated with sporadic FEVR. This study suggests that altered Norrin/β-catenin signaling is likely to be causatively involved in FEVR.
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