Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency. Invest Ophthalmol Vis Sci 2016 Jul 01;57(8):3853-63
Date
07/23/2016Pubmed ID
27447086Pubmed Central ID
PMC4968428DOI
10.1167/iovs.16-19608Scopus ID
2-s2.0-84992348116 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
PURPOSE: Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction.
METHODS: We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family.
RESULTS: There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array.
CONCLUSIONS: Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.
Author List
Patterson EJ, Wilk M, Langlo CS, Kasilian M, Ring M, Hufnagel RB, Dubis AM, Tee JJ, Kalitzeos A, Gardner JC, Ahmed ZM, Sisk RA, Larsen M, Sjoberg S, Connor TB, Dubra A, Neitz J, Hardcastle AJ, Neitz M, Michaelides M, Carroll JAuthors
Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinThomas B. Connor MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Case-Control Studies
Child
Color Vision Defects
Genetic Diseases, X-Linked
Genotype
Humans
Male
Mosaicism
Mutation
Phenotype
Retina
Retinal Cone Photoreceptor Cells
Retinal Diseases
Rod Opsins
Young Adult
