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- Title
Novel OPN1LW/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction.
- Authors
Stingl, Katarina; Baumann, Britta; De Angeli, Pietro; Vincent, Ajoy; Héon, Elise; Cordonnier, Monique; De Baere, Elfriede; Raskin, Salmo; Sato, Mario Teruo; Shiokawa, Naoye; Kohl, Susanne; Wissinger, Bernd
- Abstract
Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3–5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.
- Subjects
COLOR blindness; PHOTORECEPTORS; CONES; AMINO acid residues; VISUAL pigments; VISUAL acuity
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 12, p6868
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23126868