Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

Abstract

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.

• Authors: Emily J Patterson, Melissa Wilk, Christopher S Langlo, Melissa Kasilian, Michael Ring, Robert B Hufnagel, Adam M Dubis, James J Tee, Angelos Kalitzeos, Jessica C Gardner, Zubair M Ahmed, Robert A Sisk, Michael Larsen, Stacy Sjoberg, Thomas B Connor, Alfredo Dubra, Jay Neitz, Alison J Hardcastle, Maureen Neitz, Michel Michaelides, Joseph Carroll
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 57 Issue 8 Pg. 3853-63 (07 01 2016) ISSN: 1552-5783 [Electronic] United States
• PMID: 27447086 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Rod Opsins
• long-wavelength opsin
• middle-wavelength opsin

Topics

• Adolescent
• Adult
• Case-Control Studies
• Child
• Color Vision Defects (genetics, pathology)
• Genetic Diseases, X-Linked (genetics, pathology)
• Genotype
• Humans
• Male
• Mosaicism
• Mutation (genetics)
• Phenotype
• Retina (pathology)
• Retinal Cone Photoreceptor Cells (pathology)
• Retinal Diseases (genetics, pathology)
• Rod Opsins (genetics)
• Young Adult