eprintid: 1443934 rev_number: 40 eprint_status: archive userid: 608 dir: disk0/01/44/39/34 datestamp: 2014-09-03 18:51:54 lastmod: 2021-11-12 23:58:13 status_changed: 2014-09-03 18:51:54 type: article metadata_visibility: show item_issues_count: 0 creators_name: Gardner, JC creators_name: Liew, G creators_name: Quan, YH creators_name: Ermetal, B creators_name: Ueyama, H creators_name: Davidson, AE creators_name: Schwarz, N creators_name: Kanuga, N creators_name: Chana, R creators_name: Maher, ER creators_name: Webster, AR creators_name: Holder, GE creators_name: Robson, AG creators_name: Cheetham, ME creators_name: Liebelt, J creators_name: Ruddle, JB creators_name: Moore, AT creators_name: Michaelides, M creators_name: Hardcastle, AJ title: Three Different Cone Opsin Gene Array Mutational Mechanisms; Genotype-Phenotype Correlation and Functional Investigation of Cone Opsin Variants. ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D08 keywords: Blue Cone Monochromacy, Cone Dystrophy, OPN1LW, OPN1MW, Opsin, Splicing note: © 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. 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. date: 2014-10-28 official_url: http://dx.doi.org/10.1002/humu.22679 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: JOURNAL ARTICLE verified: verified_manual elements_source: PubMed elements_id: 972520 doi: 10.1002/humu.22679 language_elements: ENG lyricists_name: Cheetham, Michael lyricists_name: Davidson, Alice lyricists_name: Gardner, Jessica lyricists_name: Hardcastle, Alison lyricists_name: Holder, Graham lyricists_name: Michaelides, Michel lyricists_name: Moore, Anthony lyricists_name: Robson, Anthony lyricists_name: Webster, Andrew lyricists_id: MECHE52 lyricists_id: AEDAV12 lyricists_id: JGARD83 lyricists_id: AJHAR52 lyricists_id: GEHOL09 lyricists_id: MMICH14 lyricists_id: AMOOR91 lyricists_id: AROBS26 lyricists_id: ARWEB82 full_text_status: public publication: Hum Mutat volume: 35 number: 11 pagerange: 1354-1362 citation: Gardner, JC; Liew, G; Quan, YH; Ermetal, B; Ueyama, H; Davidson, AE; Schwarz, N; ... Hardcastle, AJ; + view all <#> Gardner, JC; Liew, G; Quan, YH; Ermetal, B; Ueyama, H; Davidson, AE; Schwarz, N; Kanuga, N; Chana, R; Maher, ER; Webster, AR; Holder, GE; Robson, AG; Cheetham, ME; Liebelt, J; Ruddle, JB; Moore, AT; Michaelides, M; Hardcastle, AJ; - view fewer <#> (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 <https://doi.org/10.1002/humu.22679>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1443934/1/humu22679.pdf