Identification of a novel mutation in KIF11 with functional analysis in a cohort of 516 familial patients with exudative vitreoretinopathy

PURPOSE: To identify a novel mutation in KIF11 with clinical and functional analysis among 516 familial patients with exudative vitreoretinopathy (FEVR). METHODS: Next-generation sequencing was performed on 516 patients with FEVR between January 2015 and October 2017. Clinical data were collected from patient charts, including sex, age at presentation, visual acuity if available, axial length, stage, and systemic clinical findings. Protein and mRNA levels were detected with western blotting and real-time quantitative PCR, respectively. Mass spectrometry was used to analyze the interacting protein of KIF11. RESULTS: In total, 304 of 516 patients were identified with at least one mutation in FEVR causative genes. Mutations in KIF11 were identified in 14.47% of all carriers. The novel mutation p. H718L accounted for the greatest proportion (12/44; 27.30%) among all mutations in KIF11. Fundus presentations in these 12 individuals varied from the avascular zone of the peripheral retina to total retinal detachment. The p. H718L mutation can reduce the proliferation of human retinal endothelial cells (HRECs) compared to the wild type. The mRNA level of vascular endothelial growth factor-α, transforming growth factor-α, metalloproteinase-1, and angiopoietin-like 4 were depressed in the KIF11 (p. H718L) groups under hypoxia stimuli. Mass spectrometry results demonstrated that eukaryotic elongation factor 2 (EEF2) was an interacting protein of KIF11 and that the p. H718L mutation can attenuate the binding activity. CONCLUSIONS: Patients with the most frequent KIF11 mutation p. H718L showed typical FEVR presentations in this cohort. The mutation in KIF11 likely plays a role in the proliferation of HRECs, and the p. H718L mutation can reduce the proliferation.