Genetic analysis of a large heterogeneous patient population with Familial Exudative Vitreoretinopathy

PurposeThe purpose of this study is to report the genetic findings of a large heterogeneous patient population (n=551) with the clinical diagnosis of Familial Exudative Vitreoretinopathy (FEVR). MethodsPatients (n=486) were clinically diagnosed with FEVR by exam, birth history, family history, and wide-field fluorescein angiography (WFA). Patients were excluded if WFA was not performed to confirm a proper diagnosis. DNA samples were prospectively collected and analyzed for gene mutations associated with FEVR. The patients represent a heterogenous population: 40% Michigan residents; 48% U.S. residents (non-Michigan); 12% non-U.S. residents. Specifically, alterations in NDP, FZD4, LRP5, TSPAN12, ZNF408, CTNNB1, KIF11 were evaluated. ResultsThe majority of FEVR patients (69%) had an identifiable gene mutation, with 55% of mutations affecting traditional Wnt-signaling genes: NDP 13%; FZD4 11%; LRP5 25%; TSPAN12 6%. Other affected genes represented 14% of mutations, with ZNF408 accounting for 9%. ConclusionsFEVR remains a clinical diagnosis with WFA necessary for making the diagnosis of FEVR. This database demonstrated that, with proper diagnosis, the majority of patients have a definable genetic alteration.