title: Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X.
abstract: Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes).
  
  
  
  A multigenerational family with X-linked high myopia and cone dystrophy was investigated.
  
  
  
  Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively.
  
  
  
  Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Orosz
authors.affiliation: Institute for Nuclear Research, Hungarian Academy of Sciences, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Rajta
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Vajas
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Lili
authors.initials: L
authors.lastname: Takács
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Csutak
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Mariann
authors.initials: M
authors.lastname: Fodor
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Kolozsvári
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Resch
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Sényi
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Lesch
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Szabó
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Berta
authors.affiliation: Division of Clinical Genetics, Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Balogh
authors.affiliation: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary 5Department of Ophthalmology, Zuyderland-Eyescan, Sittard-Geleen, The Netherlands.
authors.forename: Gergely
authors.initials: G
authors.lastname: Losonczy
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D017299:Rod Opsins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D017299:Rod Opsins; C095855:long-wavelength opsin; C095853:short-wavelength opsin; D004247:DNA