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Ashleigh L. Levison, Kavitha Ratnam, Austin Roorda, Stephen P. Daiger, Lori Sullivan, Sara J. Bowne, Jacque L. Duncan; High Resolution Retinal Images in a Family with Autosomal Dominant Retinitis Pigmentosa Caused By a Mutation in NR2E3. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4587. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To study structure and function in a family with autosomal dominant retinitis pigmetosa (ADRP) caused by a heterozygous mutation in the NR2E3 gene. The NR2E3 protein is a retinal transcription factor involved in differentiation and maintenance of photoreceptors.
The retinal phenotype was characterized in 2 members of a family with ADRP using visual acuity, kinetic and automated perimetry, fundus-guided microperimetry, full-field electroretinography (ERG) and spectral domain optical coherence tomography (SDOCT). Multifocal ERG and adaptive optics scanning laser ophthalmoscopy (AOSLO) were also performed in the patient with clear lenses and less advanced disease. The region of NR2E3 surrounding codon 56 (nucleotides c.150-c.210) was amplified by polymerase chain reaction (PCR) and sequenced in two directions.
A 54 year old man (P1) and his 28 year old daughter (P2) were examined. Visual acuity was 20/40 OD and 20/25 OS in P1 and 20/25 OU in P2. Visual fields in P1 were severely constricted in each eye; in P2, fields were normal to standard perimetry, but microperimetry showed relative scotomas beginning 4 degrees from fixation. Full-field ERG was unmeasurable to all stimuli in P1, but in P2 cone function was normal and rod responses were reduced. In P1, SDOCT showed loss of the outer retinal layers greater than 2.5 degrees from the fovea, with cystoid macular edema and relatively preserved outer retinal structure at the fovea; in P2, outer retinal structure was also preserved at the fovea, but there was extensive loss of the outer segment layer beyond 3 degrees, and small cysts were present within 4 degrees of fixation. P1 had cataracts and a history of refractive surgery that precluded AOSLO image acquisition. AOSLO images of the cone mosaics in P2 showed contiguous cone arrays with slightly reduced density compared to normal at and near the foveal center and patches of disrupted cones at greater eccentricities. Molecular analysis revealed a heterozygous mutation G to A substitution at nucleotide position c.166 in the NR2E3 gene in both patients, which causes a non-conservative amino acid substitution (G56R; glycine to arginine at amino acid 56) in a critical domain.
Substitution of arginine at position 56 of NR2E3 caused ADRP with cone loss in the macula. High-resolution images of cone structure demonstrate subtle cystoid macular edema and cone loss even in early disease, and could provide a sensitive measure of cone survival in patients with ADRP.
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