Background: Familial exudative vitreoretinopathy (FEVR), a group of rare inherited retinal vascular disorders, is the major cause of vision loss in juveniles. At present, the diagnosis of FEVR remains difficult due to its clinical and genetic heterogeneities. Aims: To identify the causative genetic variants in two unrelated FEVR-affected families: one Indian family and one Chinese Han family. Materials and Methods: Five affected patients from two families were recruited for this study. Whole-exome sequencing was applied to the probands, and Sanger sequencing was performed for validation. Stringent whole-exome sequence data analyses were performed to evaluate all of the identified pathogenic variants. Results: Two novel variants in the TSPAN12 gene, were identified: a missense variant c.437 T > G (p.Leu146Arg); and a nonsense variant c.477 C > A (p.Cys159*). Both variants cosegregated with the disease in the investigated FEVR-affected families. Additionally, both variants inactivated the ability of TSPAN12 protein to enhance Norrin/β-catenin signaling. Conclusion: This study expands the mutational spectrum of TSPAN12 for FEVR.
Keywords: TSPAN12; autosomal dominant FEVR; whole-exome sequencing.