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Jackie Estreicher, Tomas S. Aleman, Juan C. Zenteno, Sharon B. Schwartz, Margarita Matias-Florentino, Alejandro J. Roman, Beatriz Buentello-Volante, Alexander Sumaroka, Artur V. Cideciyan, Samuel G. Jacobson; In Vivo Retinal Pathology in Human MFRP Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2388.
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© ARVO (1962-2015); The Authors (2016-present)
To test hypotheses about disease mechanisms in human retinopathy caused by mutations in the MFRP (membrane-type frizzled related protein) gene.
Genomic DNA was obtained; the 13 exons of the MFRP gene were PCR-amplified; and direct nucleotide sequencing was performed. Retinal/visual function was measured with ERG and chromatic static perimetry. RPE health was evaluated with autofluorescence (AF) imaging. Retinal cross-sections were acquired with SD-OCT and quantified.
Two MFRP mutations (c. 498delC in exon 5 and a novel intron 9 splice site mutation) were identified in a 19 yr-old female patient. There was high hyperopia (+11.00; axial length, 16.4mm) and there were fundus features of pigmentary retinopathy. Visual acuities were 20/30. Rod and cone function was abnormally reduced by ERG and psychophysics. RPE dysfunction due to this mutant RPE gene was not detectable. Specifically, there was no evidence of a phagocytosis defect or a visual cycle abnormality: retinal regions with measurable OS showed no difference in OS layer thickness versus normal, and, the relationship of rod function and photoreceptor structure followed a model expected from photoreceptor degenerations. Central retinal architecture was abnormal with greatly increased central retinal thickness, inner nuclear layer schisis, absence of a foveal depression, and inner retinal structures present across what would normally be the foveal region. ONL thickness decreased with eccentricity while the inner retina was hyper-thick. AF imaging was consistent with a ~20° diameter central region of retained RPE with normal lipofuscin and melanin signals obtained with short-wavelength (SW) or near-infrared (NIR) AF imaging, respectively. Optic disc drusen were detectable on SW-AF.
MFRP mutations have been associated with nanophthalmos and retinal degeneration. Doming in the central retina with persistent inner retinal structure across the presumptive fovea in human MFRP disease suggests a disturbance in the complex cell migrations that lead to normal foveal development.
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