Abstract
PURPOSE: To report the novel causative variants in five Chinese families with familial exudative vitreoretinopathy (FEVR). METHODS: Five unrelated Chinese families diagnosed with FEVR were enrolled in this study. Ocular examinations and genetic analysis were performed on the probands and family members. Luciferase assay was performed to evaluate the variants' impacts on Norrin/β-catenin signaling activity. RESULTS: Five novel variants, including two frameshifts, c.518delA (p.Glu173Glyfs*42) and c.719delT (p.Leu240Profs*21), two missenses, c.482G>T (p.Gly161Val) and c. 614G>C (p. Gly205Ala), and one nonsense, c.375G>A (p.Trp125*), were identified in the TSPAN12 gene in this study. All the variants were co-segregated within each family and were predicted as pathogenic in silico. The luciferase assay showed all variants lead to various degrees of compromised Norrin/β-catenin signaling activity. CONCLUSIONS: Our study expanded the variant spectrum and provided information for the genetic testing of FEVR by showing five novel FEVR-associated pathogenic variants in TSPAN12. TRANSLATIONAL RELEVANCE: Our study expanded the spectrum of FEVR-associated TSPAN12 variants and further supported the inclusion of TSPAN12 gene in the evaluation of cases concerning for FEVR.