Academic Journal
Blue cone monochromacy with parafoveal hyperautofluorescent ring caused by a novel OPN1LW p.Ile109Asn variant.
| Τίτλος: | Blue cone monochromacy with parafoveal hyperautofluorescent ring caused by a novel OPN1LW p.Ile109Asn variant. |
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| Συγγραφείς: | Huang J; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Brodie SE; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA., Kong J; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA., Soucy M; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA., Maumenee IH; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA., Tsang SH; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA. sht2@cumc.columbia.edu.; Jonas Children's Vision Care, Columbia Stem Cell Initiative, Departments of Ophthalmology, Pathology and Cell Biology, Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. sht2@cumc.columbia.edu. |
| Πηγή: | Documenta ophthalmologica. Advances in ophthalmology [Doc Ophthalmol] 2026 Oct; Vol. 153 (2), pp. 289-295. Date of Electronic Publication: 2026 Jun 11. |
| Τύπος έκδοσης: | Journal Article; Case Reports |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Kluwer Country of Publication: Netherlands NLM ID: 0370667 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2622 (Electronic) Linking ISSN: 00124486 NLM ISO Abbreviation: Doc Ophthalmol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Dordrecht : Kluwer Original Publication: s'-Gravenhage [etc.] |
| Ιατρικοί όροι (MeSH): | Rod Opsins*/genetics , Rod Opsins*/metabolism , Color Vision Defects*/genetics , Color Vision Defects*/diagnosis , Color Vision Defects*/metabolism , Fovea Centralis*/pathology , Retinal Cone Photoreceptor Cells*/pathology , DNA*/genetics , Mutation, Missense*, Humans ; Male ; Child ; Electroretinography ; Tomography, Optical Coherence ; Fluorescein Angiography ; Visual Acuity ; DNA Mutational Analysis ; Fundus Oculi ; Pedigree |
| Περίληψη: | Background: Blue Cone Monochromacy is a rare X-linked retinal disorder characterized by the selective loss of long-(L) and medium-(M) wavelength-sensitive cone function. While typically caused by large-scale genomic deletions or rearrangements within the OPN1LW/OPN1MW gene cluster, missense mutations are less common. Because blue cone monochromacy is often considered a stationary, congenital condition, sporadic cases lacking a family history can often be misidentified. Case Presentation: A 12-year-old boy presented with reduced visual acuity and a parafoveal hyperautofluorescent ring pattern on fundus autofluorescence and was initially referred for work-up of CRX-related maculopathy. However, electroretinography (ERG) revealed preserved S-cone and rod function with moderately reduced photopic responses. Genetic sequencing identified a novel, maternally inherited, hemizygous missense mutation in the gene encoding OPN1LW (c.326T > A; p.Ile109Asn). AlphaFold simulations demonstrated that the substitution disrupts the 11-cis-retinal binding pocket by altering the hydrogen bonding network near the critical Lys312 residue. This structural instability likely impairs the phototransduction cascade and delays chromophore clearance, contributing to localized foveal photoreceptor stress and the observed macular structural changes. Conclusions: This report identifies a novel OPN1LW missense variant and provides a mechanistic basis for its pathogenicity through advanced structural modeling. Our findings demonstrate that blue cone monochromacy can present with atypical, progressive-appearing macular features, potentially mimicking Stargardt disease or other maculopathies. Furthermore, this case highlights the utility of in silico protein modeling in bridging the gap between variants and clinical phenotypes, expanding the known molecular spectrum of X-linked cone disorders. (© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. Human Rights Statement: This article does not contain any studies with human participants performed by any of the authors beyond routineclinical care. All procedures were in accordance with the ethical standards of the institutional and/or nationalresearch committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethicalstandards. Animal Welfare Statement: This article does not contain any studies with animals performed by any of the authors. Informed Consent: Formal informed consent was not obtained for publication. However, all clinical data and images have been fullyanonymized, and no identifi able patient information is included in this case report. |
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| Contributed Indexing: | Keywords: OPN1LW; AlphaFold simulation; Blue cone monochromacy; Bull’s-eye maculopathy; Cone dystrophy; Missense mutation |
| Substance Nomenclature: | 0 (Rod Opsins) 0 (long-wavelength opsin) 9007-49-2 (DNA) |
| SCR Disease Name: | Blue cone monochromatism |
| Entry Date(s): | Date Created: 20260611 Date Completed: 20260928 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s10633-026-10118-6 |
| PMID: | 42274835 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-2622 |
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| DOI: | 10.1007/s10633-026-10118-6 |