title: A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses.
abstract: OBJECTIVE
  The only mutations reported to date in Japanese patients with Oguchi disease, a rare form of stationary night blindness with autosomal recessive transmission, have been in the SAG (arrestin) gene. The objective of this study was to describe the ophthalmic features and a novel mutation in the GRK1 (rhodopsin kinase) gene in 2 Japanese patients with Oguchi disease.
  
  
  METHODS
  Molecular genetic and observational case study.
  
  
  METHODS
  A consanguineous family including 2 siblings with Oguchi disease (a 35-year-old man and a 31-year-old woman).
  
  
  METHODS
  Best-corrected visual acuity (BCVA), fundus examinations, Goldmann perimetry, color vision tests, and full-field electroretinograms (ERGs) were evaluated. Mutation screening of the SAG and GRK1 genes was performed with polymerase chain reaction amplification and direct sequencing.
  
  
  METHODS
  Mutations in the GRK1 gene, BCVA, color vision, fundus photographs, visual fields, and ERG findings.
  
  
  RESULTS
  Molecular analysis revealed a novel homozygous missense mutation (p.P391H) in the GRK1 gene in both patients. Proline 391 is not only within the functionally important catalytic domain, but is also a phylogenetically conserved amino acid residue among GRK1 orthologs and homologs. No mutation was found in the SAG gene. The unaffected parents were heterozygous carriers of the mutation. Both patients had night blindness, 1.5 BCVA for each eye, normal color vision, and typical fundus appearance with golden-yellow discoloration. The visual fields were normal in the male sibling. The ERGs showed no rod B waves, reduced standard combined responses, and markedly reduced single-flash cone and 30-Hz flicker responses in both patients.
  
  
  CONCLUSIONS
  A novel homozygous GRK1 mutation (p.P391H) was found in 2 Japanese siblings with Oguchi disease. Visual function in the 2 patients has not deteriorated with age, indicating that the disease is stationary. This is the first report of any patient with GRK1-associated Oguchi disease with markedly reduced cone responses.
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan. taka@jikei.ac.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Tamaki
authors.initials: T
authors.lastname: Gekka
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Goto-Omoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitahara
mesh_terms: D000328:Adult; D019393:Arrestin / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009755:Night Blindness / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology*; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D035781:Siblings; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D019393:Arrestin; D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human