Abstract
PURPOSE: Familial exudative vitreoretinopathy (FEVR) is an inherited vitreoretinopathy. This study aimed to analyze the ocular phenotypes and systemic features of patients with CTNNB1 mutations. METHODS: Whole exome sequencing was performed in the probands, and Sanger sequencing was used to verify the mutations and perform segregation analysis in the available family members. A luciferase assay was used to assess the effect of the mutant β-catenin on transcription. Comprehensive ocular examinations were performed on the probands and family members. Systemic features were evaluated and followed up. RESULTS: A total of 763 FEVR families were enrolled. Seven different CTNNB1 mutations, including 5 novels and 2 known mutations, were detected in 8 families, accounting for 1.05% of all FEVR families. Compared to wild-type CTNNB1, the CTNNB1 mutants failed to induce luciferase reporter activity in SuperTopFlash (STF) cells. Among the 16 eyes of the 8 probands, 2 (12.5%) eyes were classified as stage 2 FEVR, 8 (50.0%) as stage 4, and 6 (37.5%) as stage 5. All the patients had varying degrees of systemic abnormalities and presented with motor, speech, and developmental delays over time. Among the eight families with CTNNB1 mutations, seven were de novo mutations, and one proband inherited the mutation from his asymptomatic mother. CONCLUSIONS: This study provides detailed descriptions of the ocular phenotypes of patients with CTNNB1 mutations that presented as severe FEVR, and accompanied with other systemic abnormalities. Five novel mutations identified in this study, expanded the mutation spectrum of CTNNB1-associated FEVR.