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Three Different Cone Opsin Gene Array Mutational Mechanisms; Genotype-Phenotype Correlation and Functional Investigation of Cone Opsin Variants.

Gardner, JC; Liew, G; Quan, YH; Ermetal, B; Ueyama, H; Davidson, AE; Schwarz, N; ... Hardcastle, AJ; + view all (2014) Three Different Cone Opsin Gene Array Mutational Mechanisms; Genotype-Phenotype Correlation and Functional Investigation of Cone Opsin Variants. Hum Mutat , 35 (11) pp. 1354-1362. 10.1002/humu.22679. Green open access

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Abstract

Mutations in the OPN1LW (L-) and OPN1MW (M-) cone opsin genes underlie a spectrum of cone photoreceptor defects from stationary loss of colour vision to progressive retinal degeneration. Genotypes of 22 families with a range of cone disorders were grouped into three classes: deletions of the Locus Control Region (LCR); missense mutation (p.Cys203Arg) in an L-/M- hybrid gene; and exon 3 single nucleotide polymorphism (SNP) interchange haplotypes in an otherwise normal gene array. Moderate to high myopia was observed in all mutation categories. Individuals with LCR deletions or p.Cys203Arg mutations were more likely to have nystagmus and poor vision, with disease progression in some p.Cys203Arg patients. Three disease-associated exon 3 SNP haplotypes encoding LIAVA, LVAVA or MIAVA, were identified in our cohort. These patients were less likely to have nystagmus but more likely to show progression, with all patients over the age of 40 having marked macular abnormalities. Previously, the haplotype LIAVA has been shown to result in exon 3 skipping. Here we show that haplotypes LVAVA and MIAVA also result in aberrant splicing, with a residual low level of correctly spliced cone opsin. The OPN1LW/OPN1MW:c.532A>G SNP, common to all three disease-associated haplotypes, appears to be principally responsible for this mutational mechanism. This article is protected by copyright. All rights reserved.

Type: Article
Title: Three Different Cone Opsin Gene Array Mutational Mechanisms; Genotype-Phenotype Correlation and Functional Investigation of Cone Opsin Variants.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/humu.22679
Publisher version: http://dx.doi.org/10.1002/humu.22679
Language: English
Additional information: © 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: Blue Cone Monochromacy, Cone Dystrophy, OPN1LW, OPN1MW, Opsin, Splicing
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1443934
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