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Saoud A Al-khuzaei, Stephanie Halford, Penny Clouston, Robert E MacLaren, Susan M. Downes; Genotype-Phenotype Analysis of Three Novel NR2E3 Mutations. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2933.
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© ARVO (1962-2015); The Authors (2016-present)
NR2E3 is a crucial gene for the development and maintenance of rod and cone cells in the retina. Mutations in this gene are rare and patients can present with a variety of phenotypes. Patients with recessive mutations can be affected by Enhanced S Cone Syndrome, Goldman-Favre Syndrome, and clumped pigmentary retinal degeneration, whilst dominant mutations have a similar phenotypic appearance to retinitis pigmentosa. In this study, we describe the phenotypic retinal appearance of three patients with novel mutations.
Data on patients with NR2E3 mutations was retrospectively reviewed to obtain a cohort of eight patients. We reviewed the clinical course, fundus features, visual field results, electroretinogram (ERG) results. The genetic analysis results were obtained using the HaloPlex Target Enrichment system. In silico analysis using three different methods was then used to determine the deleteriousness of the variants. Three patients were excluded because their phenotypes were consistent with other gene mutations.
Three novel NR2E3 mutations were identified in three patients; c.1048C>G (p.Gln350Glu), c.755T>C (p.Leu252Pro) and c.639_640insT(p.Pro214Serfs). A compound heterozygous patient for c.119-2A>C and a novel c.639_640insT(p.Pro214Serfs) mutation had a fundus with white punctate dots at the mid-peripheral retina, these dots were circumferential to the macula and associated with mid-peripheral loss in the 10 degrees to 40 degrees of vision, the ERG identified that the rods were more severely affected than cones and the inner retinal function was more affected than the photoreceptors with relative sparing of the macula. Examination of the compound heterozygous patient for c.226C>T(p.Arg76Trp) and a novel c.1048C>G (p.Gln350Glu) mutation identified heavily pigmented retinas, autofluorescence imaging showed significant widespread atrophic changes from the arcades to the mid-periphery and visual fields were less than 5 degrees. One patient was homozygous for the novel c.755T>C, p.(Leu252pro) mutation. Examination identified bilateral annular degeneration around the arcades and a dense central scar. ERG testing showed significant rod, cone and macula dysfunction.
We identified three novel NR2E3 mutations that had an autosomal recessive inheritance pattern. This study highlights the importance of genetic analysis for identifying patients with NR2E3 mutations due to its rarity and variable phenotype.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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