Variant in EZR leads to defects in lens development

ABSTRACT

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.

KEYWORDS:

• Congenital cataract
• ezrin
• mutation
• zebrafish

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Authors’ contributions

Nan Zhou: Conceptualization, Methodology, Reviewing and Editing, Fun ding. Mingyan He: Methodology, Data curation, original draft preparation. Guangkai Zhou: Visualization, Investigation. Qiuyang Fan: Tables, Figures. Yanhua Qi: Supervision. All authors reviewed the manuscript.

Consent to participate

Written informed consent was obtained from individual or guardian participants.

Ethics approval

The clinical and experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Harbin Medical University.

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2024.2330391

Additional information

Funding

This study supported by National Natural Science Foundation of China [grant numbers 81200667].