A Novel Frameshift Variant in KIF11 Causes Autosomal Dominant Familial Exudative Vitreoretinopathy in a Chinese Family.

Background

Familial exudative vitreoretinopathy (FEVR) is a rare inherited ocular disorder characterized by abnormal peripheral retinal vascular development. KIF11 variants are known to cause autosomal dominant FEVR, but novel pathogenic variants remain to be identified.

Objective

This study aimed to identify a novel causative variant of FEVR and provide evidence for genetic counseling.

Methods

Whole-exome sequencing was performed on members of a Chinese family with FEVR. Rare variants with a gnomAD allele frequency <0.1% in East Asian and general populations were prioritized. Sanger sequencing was used for validation, and bioinformatic analyses (including Combined Annotation Dependent Depletion [CADD] score and cross-species conservation analysis) were conducted to assess pathogenicity.

Results

A novel heterozygous frameshift variant KIF11 c.1239_1240del (p.V414Sfs*9) was identified in the proband, his brother, and his mother. This variant, absent from public databases (1000 Genomes, ExAC, gnomAD), had a CADD score of 26.9 and affected a highly conserved residue, suggesting disruptive effects on protein structure. The proband's mother showed macular involvement.

Conclusions

The novel KIF11 frameshift variant (c.1239_1240del p.V414Sfs*9) identified in a Chinese family expands the mutation spectrum of autosomal dominant FEVR, with macular involvement aiding clinical prognostic assessment.