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Hiroyuki Kondo, Eiichi Uchio, Takaaki Hayashi, Sachiko Nishina, Noriyuki Azuma, Shunji Kusaka; Roles of genes in phenotypic diversity and intraocular asymmetry in patients with familial exudative vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2626.
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© 2017 Association for Research in Vision and Ophthalmology.
The severity of familial exudative vitreoretinopathy (FEVR) is diverse and asymmetrical between the two eyes. The roles played by the genes associated with FEVR on this phenotypic diversity and asymmetry remain undetermined. The purpose of this study was to compare the frequencies of each gene associated with specific phenotypes among FEVR patients with different severities and asymmetries of the retinal phenotypes.
We examined the phenotypes of 153 unrelated probands with FEVR including Norrie disease-like phenotype. The ocular features were classified into 5 groups: (G1) retinal vascular anomalies with or without neovascularization, (G2) dragged macula, (G3) falciform retinal fold, (G4) rhegmatogenous or exudative retinal detachment, and (G5) leukocoria with a total retinal detachment. For the asymmetries, the severities were further subdivided into G5(one eye)/1..5(opposite eye), G4/1..4, G3/1..3, G2/1..2, and G1/1. A mutation search was performed on the probands for the known FEVR-causing genes (FZD4, LRP5, TSPAN12, NDP, and ZNF408) by Sanger sequencing. The detection frequencies were compared among these groups.
The mutation detection rate for one of the 5 genes was 42% (65/154). The detection rate of genes FZD4, LRP5, TSPAN12, NDP, and ZNF408, and their combinations were 42%, 26%, 11%, 15%, 2%, and 5%, respectively. Higher detection rates were found in groups of G3/2 (77%), G5/5 (75%), and G2/2 (70%). Mutations in NDP were identified exclusively in the G5/5 group concordant with a diagnosis of Norrie disease. Lower detections were observed in groups with mild vascular changes in at least one eye as G1/1 (16%), G2/1 (35%), and G4/1 (38%). No mutations were detected in group G5/1 and G4/4. No gene preponderance was found among the groups other than in the G5/5 group.
These findings indicate that mutations in known FEVR genes would be less detected if the retinal changes of the probands were restricted to mild vascular changes in both eyes. Known genes except for NDP rarely cause bilateral leukocoria. The etiology of unilateral leukocoria with mild vascular changes in the fellow eye (G5/1) may be different from known FEVR genes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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