title: Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Patterson
authors.affiliation: Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wilk
authors.affiliation: Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Langlo
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kasilian
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Ring
authors.affiliation: Department of Pediatrics, Division of Pediatric Ophthalmology, University of Cincinnati and Cincinnati Children's Hospital, Cincinnati, Ohio, United States.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Dubis
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Tee
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Angelos
authors.initials: A
authors.lastname: Kalitzeos
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Gardner
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, United States.
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.affiliation: Department of Pediatrics, Division of Pediatric Ophthalmology, University of Cincinnati and Cincinnati Children's Hospital, Cincinnati, Ohio, United States.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sisk
authors.affiliation: Department of Ophthalmology, Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Great River Eye Clinic, Crosby, Minnesota, United States.
authors.forename: Stacy
authors.initials: S
authors.lastname: Sjoberg
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Connor
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 9Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 10Department of Cell Biology, Neurobiology, & Anatomy, Medical Coll.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Jay
authors.initials: J
authors.lastname: Neitz
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Maureen
authors.initials: M
authors.lastname: Neitz
authors.affiliation: UCL Institute of Ophthalmology, London, United Kingdom 4Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 9Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 10Department of Cell Biology, Neurobiology, & Anatomy, Medical Coll.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003117:Color Vision Defects / Q000235:genetics* / Q000473:pathology; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000473:pathology*; D005838:Genotype; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012160:Retina / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012164:Retinal Diseases / Q000235:genetics / Q000473:pathology*; D017299:Rod Opsins / Q000235:genetics*; D055815:Young Adult
chemical_list: D017299:Rod Opsins; C095855:long-wavelength opsin; C095854:middle-wavelength opsin