Genotypes-phenotype correlation in familial exudative vitreoretinopathy probands with KIF-11 mutation

Abstract

Purpose : KIF-11 gene mutation has been newly reported to be a cause of familial exudative vitreoretinopathy (FEVR) while the genotype-phenotype correlation is still under investigation. We performed a retrospective study of the FEVR probands with KIF-11 gene mutation to learn about the genotype-phenotype correlation.

Methods : Clinical and genetic data of 78 patients diagnosed with FEVR during 2013 to 2015 were reviewed. All the patients had undergone genetic analysis of FZD4, LRP5, TSPAN12, ZNF408, and KIF-11 gene by Sanger sequencing. The patients with KIF-11 gene mutation were studied and followed up for longer than 6 months.

Results : KIF-11 gene mutation was discovered in 16 of the 78 probands with FEVR, including heterozygous point mutation (n= 13 probands) in c.2153A>T (p.H718L)(n=10), c.1924C>G (p.P642A)(n=1),c.2807C>G (p.S936X)(n=2),heterozygous splicing mutation in c.790-2A>C(n=1), heterozygous deletion in c.2949d elG (n=1), and heterozygous whole gene deletion (n=1). Of the 16 patients, there were 10 males and 6 females, aging from 8 months to 8 years old. The follow-up time ranged from 6 months to 24 months.All the patients had typical bilateral vitreoretinopathies diagnostic of FEVR and symmetrical staging of the disease was observed in 7 at first visit. Except for 1 patient with c.2153A>T mutation having mild peripheral retinal avascularity, the remaining 12 with point mutation had falciform retinal folds(n=5) and total retinal detachment(n=7) and 7 of them were undergoing disease progression.(Fig 1, 2) Two patients with gene deletion had progressive bilateral tractional retinal detachment and 1 of them developed elevated intraocular pressure due to pupil occlusion. One patient with gene splicing had bilateral falciform folds with repeately hemorrhage in one eye. Treatment was performed in 6 patients involving anti-glaucoma theraphy, retinal photocoagulation,anti-VEGF therapy,and staged vitrectomy, although 4 patients were still undergoing exacerbation.

Conclusions : FEVR probands affecting KIF-11 gene mutation are predisposed to progressive and severe ocular phenotypes and the heterozygous point mutation in KIF-11 gene is the predominant genotype.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Figure 1. Fluroscein angiogram of a boy infant with FEVR. Dilated vessel endings and extensive avascular zone with profuse leakage.

 

Figure 2. Falciform fold was formed 6 months after the first visit, even after timely laser treatment.