Three Different Cone Opsin Gene Array Mutational Mechanisms with Genotype–Phenotype Correlation and Functional Investigation of Cone Opsin Variants. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Gardner, Jessica C.; Liew, Gerald; Quan, Ying‐Hua; Ermetal, Burcu; Ueyama, Hisao; Davidson, Alice E.; Schwarz, Nele; Kanuga, Naheed; Chana, Ravinder; Maher, Eamonn R.; Webster, Andrew R.; Holder, Graham E.; Robson, Anthony G.; Cheetham, Michael E.; Liebelt, Jan; Ruddle, Jonathan B.; Moore, Anthony T.; Michaelides, Michel; Hardcastle, Alison J.
• Is Part Of: Human mutation. Volume 35:Issue 11(2014:Nov.)
• Page Start: 1354
• Page End: 1362
• Publication Date: 2014-11
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22679
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Mutations in the <italic>OPN1LW</italic> (L‐) and <italic>OPN1MW</italic> (M‐)cone opsin genes underlie a spectrum of cone photoreceptor defects from stationary loss of color 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 years 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 <italic>OPN1LW</italic>/<italic>OPN1MW</italic>:c.532A&gt;G SNP, common to all three disease‐associated haplotypes, appears to be principally responsible for this mutational mechanism.</p> </abstract>