Investigating the mutation spectrum for Familial Exudative Vitreoretinopathy (FEVR)

Familial exudative vitreoretinopathy (FEVR) is a rare inherited retinal eye disease, which can lead to vision loss or total blindness. It is characterized by abnormal development of blood vessels in the retina, which may trigger neovascularization leading to retinal folds and detachment. FEVR is genetically heterogeneous with eleven genes reported to date (NDP, FZD4, LRP5, TSPAN12, CTNNB1, KIF11, ZNF408, ATOH7, RCBTB1, JAG1 and ILK) and an ever-increasing number of variants being reported in these. This project focused on generating a mutation database and spectrum for FEVR. Variant information was gathered either from unpublished data from the Toomes’ lab or from peer-reviewed journal articles. All of the mutations were annotated so that they complied with the latest Human Genome Variation Society nomenclature and were uploaded onto the Leiden Open Variation Database. Pathogenicity classifications of variants were reassessed using the latest pathogenic prediction tools and frequency data and were classified according to the American College of Medical Genetics (ACMG) guidelines. In addition, missense mutant protein structures were predicted using Modeller9.24 software and compared with the correspondent wildtype protein model using UCSF chimera to attempt to highlight differences to aid in variant classification.