Variant in EZR leads to defects in lens development.

Background: Congenital cataract is a common cause of blindness. Genetic factors always play important role.

Material and methods: This study identified a novel missense variant (c.1412C>T (p.P471L)) in the EZR gene in a four-generation Chinese family with nuclear cataract by linkage analysis and whole-exome sequencing. A knockout study in zebrafish using transcription activator-like effector nucleases was carried out to gain insight into candidate gene function.

Results: Conservative and functional prediction suggests that the P-to-L substitution may impair the function of the human ezrin protein. Histology showed developmental delays in the ezrin-mutated zebrafish, manifesting as multilayered lens epithelial cells. Immunohistochemistry revealed abnormal proliferation patterns in mutant fish.

Conclusions: The study suggests that ezrin may be involved in the enucleation and differentiation of lens epithelial cells.