Update on the Phenotypic and Genotypic Spectrum of

Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25/696). Among 25 KIF11 mutations, 80% (20/25) carried variants of loss of function and 48% (12/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1/70) of eyes with FEVR with mutations in other genes (p < 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12/70) of eyes with KIF11-associated retinopathy, and in 50% (39/78) of eyes with FEVR with mutations in other genes (p < 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.