title: Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy.
abstract: OBJECTIVE
  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.
authors: University College London Institute of Ophthalmology, London, United Kingdom.
authors: Michelle
authors: M
authors: McClements
authors: Wayne I L
authors: WI
authors: Davies
authors: Michel
authors: M
authors: Michaelides
authors: Terri
authors: T
authors: Young
authors: Maureen
authors: M
authors: Neitz
authors: Robert E
authors: RE
authors: MacLaren
authors: Anthony T
authors: AT
authors: Moore
authors: David M
authors: DM
authors: Hunt
mesh_terms: D000293:Adolescent; D000328:Adult; D003117:Color Vision Defects / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004596:Electroretinography; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009216:Myopia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D017299:Rod Opsins / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome; D055815:Young Adult
chemical_list: D017299:Rod Opsins; D004247:DNA