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Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy.

Publication ,  Journal Article
McClements, M; Davies, WIL; Michaelides, M; Young, T; Neitz, M; MacLaren, RE; Moore, AT; Hunt, DM
Published in: Invest Ophthalmol Vis Sci
February 15, 2013

PURPOSE: To determine the role of variant L opsin haplotypes in seven families with Bornholm Eye Disease (BED), a cone dysfunction syndrome with dichromacy and myopia. METHODS: Analysis of the opsin genes within the L/M opsin array at Xq28 included cloning and sequencing of an exon 3-5 gene fragment, long range PCR to establish gene order, and quantitative PCR to establish gene copy number. In vitro expression of normal and variant opsins was performed to examine cellular trafficking and spectral sensitivity of pigments. RESULTS: All except one of the BED families possessed L opsin genes that contained a rare exon 3 haplotype. The exception was a family with the deleterious Cys203Arg substitution. Two rare exon 3 haplotypes were found and, where determined, these variant opsin genes were in the first position in the array. In vitro expression in transfected cultured neuronal cells showed that the variant opsins formed functional pigments, which trafficked to the cell membranes. The variant opsins were, however, less stable than wild type. CONCLUSIONS: It is concluded that the variant L opsin haplotypes underlie BED. The reduction in the amount of variant opsin produced in vitro compared with wild type indicates a possible disease mechanism. Alternatively, the recently identified defective splicing of exon 3 of the variant opsin transcript may be involved. Both mechanisms explain the presence of dichromacy and cone dystrophy. Abnormal pigment may also underlie the myopia that is invariably present in BED subjects.

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Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 15, 2013

Volume

54

Issue

2

Start / End Page

1361 / 1369

Location

United States

Related Subject Headings

  • Young Adult
  • Syndrome
  • Rod Opsins
  • Retinitis Pigmentosa
  • Retinal Cone Photoreceptor Cells
  • Polymerase Chain Reaction
  • Pedigree
  • Ophthalmology & Optometry
  • Myopia
  • Male
 

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McClements, M., Davies, W. I. L., Michaelides, M., Young, T., Neitz, M., MacLaren, R. E., … Hunt, D. M. (2013). Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy. Invest Ophthalmol Vis Sci, 54(2), 1361–1369. https://doi.org/10.1167/iovs.12-11156
McClements, Michelle, Wayne I. L. Davies, Michel Michaelides, Terri Young, Maureen Neitz, Robert E. MacLaren, Anthony T. Moore, and David M. Hunt. “Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy.Invest Ophthalmol Vis Sci 54, no. 2 (February 15, 2013): 1361–69. https://doi.org/10.1167/iovs.12-11156.
McClements M, Davies WIL, Michaelides M, Young T, Neitz M, MacLaren RE, et al. Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy. Invest Ophthalmol Vis Sci. 2013 Feb 15;54(2):1361–9.
McClements, Michelle, et al. “Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy.Invest Ophthalmol Vis Sci, vol. 54, no. 2, Feb. 2013, pp. 1361–69. Pubmed, doi:10.1167/iovs.12-11156.
McClements M, Davies WIL, Michaelides M, Young T, Neitz M, MacLaren RE, Moore AT, Hunt DM. Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy. Invest Ophthalmol Vis Sci. 2013 Feb 15;54(2):1361–1369.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 15, 2013

Volume

54

Issue

2

Start / End Page

1361 / 1369

Location

United States

Related Subject Headings

  • Young Adult
  • Syndrome
  • Rod Opsins
  • Retinitis Pigmentosa
  • Retinal Cone Photoreceptor Cells
  • Polymerase Chain Reaction
  • Pedigree
  • Ophthalmology & Optometry
  • Myopia
  • Male