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Xianjun Zhu, Periasamy Sundaresan, Yu Zhou, Xiong Zhu; TSPAN12 mutation spectrum of a cohort of Familial Exudative Vitreoretinopathy patients. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2900.
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© ARVO (1962-2015); The Authors (2016-present)
Familial exudative vitreoretinopathy (FEVR) is a group of inherited retina diseases characterized by defective retinal vessels. Tetraspanin 12 (TSPAN12) was identified as a cause of FEVR in several genetic studies. The purpose of this study was to identify novel TSPAN12 mutations in a cohort of India patients with FEVR and to describe the associated clinical phenotypes.<br />
Written consent was obtained form all subjects in this study. Clinical phenotypes of the patients with TSPAN12 mutations were documented.Whole exome sequencing was applied to a cohort of 27 families of FEVR patients. All variants were verified by Sanger sequencing. Effect of geteic variants on protein funcyion were pridicted by SIFT and Polyphen spoftware. Effects of idenfied mutations on TSPAN12 protein function were assayed for the Norrin-β-catenin signaling pathway with luciferase reporter assays.<br /> <br />
Five novel heterozygous mutations in TSPAN12 were identified. All mutations involved highly conserved residues and were not present in 500 normal individuals. In SuperTopFlash (STF) cell line, four of these mutants failed to induce luciferase reporter activity in response to Norrin.<br />
Five novel TSPAN12 mutations in India patients with autosomal dominant FEVR were identified. Similar to that of FZD4 and LRP5, the phenotypes associated with TSPAN12 mutations showed variation in disease severity among members of the same family.
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