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Arundhati Dev Borman, Louise Ocaka, Donna S. Mackay, Caterina Ripamonti, Anthony G. Robson, Graeme Black, Andrew R. Webster, Fred Fitzke, Andrew Stockman, Anthony T. Moore; Childhood Onset Retinal Dystrophy Due To LRAT Mutations. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5380.
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© ARVO (1962-2015); The Authors (2016-present)
To delineate the phenotype in Leber's congenital amaurosis or autosomal recessive severe childhood onset retinal dystrophy (EORD) due to mutations in the Lecithin Retinol Acyltransferase (LRAT) gene.
LRAT mutations were identified via an Arrayed Primer Extension (APEX) genotyping microarray (Asper Ophthalmics) or Sanger sequencing. Patients were examined and where possible, underwent autofluorescence imaging, spectral domain optical coherence tomography (OCT), International-standard pattern and full-field electroretinography (PERG; ERG), dark adapted perimetry and psychophysical assessments of photoreceptor (PR) function.
APEX analysis identified 1 patient with a known homozygous LRAT mutation. 3 further patients with novel homozygous mutations were identified via sequencing a panel of 148 EORD patients, in whom known variants had been excluded. 4/4 patients had severe nyctalopia and visual field constriction from age 1-2 years. In 3/4, 'light staring' was prominent in childhood. All reported deterioration with time. Visual acuity varied from 6/9.5 to hand movements. All had severe RPE atrophy and minimal intra-retinal pigmentation. 2 had asteroid hyalosis and 2 had macular epi-retinal membranes. All had low levels of macular autofluorescence. OCT showed retinal thinning and a retained foveal PR outer segment layer in 3/3 patients. ERGs were undetectable in 1/3 or showed severe rod-cone dysfunction in 2/3; PERGs indicated severe macular involvement. Dark adapted perimetry in 3/3 showed some retained function but severely reduced sensitivities to blue and red stimuli. Dark-adapted spectral sensitivity measurements revealed functioning rods in 2/3 patients. All 3 had severely reduced L- and M-cone sensitivity, no measureable S-cone sensitivity and very poor colour discrimination.
LRAT mutations cause a severe progressive retinal dystrophy from childhood. There is residual photoreceptor function in adulthood, which may provide a window of opportunity for therapeutic intervention until early adult life.
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