{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T22:45:54Z","timestamp":1769208354817,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Wi1189\/12-1"],"award-info":[{"award-number":["Wi1189\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u20135% 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.<\/jats:p>","DOI":"10.3390\/ijms23126868","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T01:43:27Z","timestamp":1655775807000},"page":"6868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel OPN1LW\/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-911X","authenticated-orcid":false,"given":"Katarina","family":"Stingl","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Baumann","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-551X","authenticated-orcid":false,"given":"Pietro","family":"De Angeli","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6446-3846","authenticated-orcid":false,"given":"Ajoy","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"H\u00e9on","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Cordonnier","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, H\u00f4pital Erasme, Cliniques Universitaires de Bruxelles, Universit\u00e9 Libre de Bruxelles, 1070 Bruxelles, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-6895","authenticated-orcid":false,"given":"Elfriede","family":"De Baere","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Ghent University Hospital, Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salmo","family":"Raskin","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Genetika, Curitiba 80730-180, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario Teruo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Otorhinolaryngology, Federal University of Paran\u00e1, Curitiba 80060-900, Brazil"},{"name":"Retina and Vitreo Consulting Eye Clinic, Curitiba 80530-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoye","family":"Shiokawa","sequence":"additional","affiliation":[{"name":"Retina and Vitreo Consulting Eye Clinic, Curitiba 80530-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-6331","authenticated-orcid":false,"given":"Susanne","family":"Kohl","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-5953","authenticated-orcid":false,"given":"Bernd","family":"Wissinger","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1126\/science.2937147","article-title":"Molecular genetics of human color vision: The genes encoding blue, green, and red pigments","volume":"232","author":"Nathans","year":"1986","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1073\/pnas.022629799","article-title":"Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes","volume":"99","author":"Smallwood","year":"2002","journal-title":"Proc. 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