PURPOSE: 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. DESIGN: Molecular genetic and observational case study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
PURPOSE: 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. DESIGN: Molecular genetic and observational case study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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: Hanna Västinsalo; Reetta Jalkanen; Astra Dinculescu; Juha Isosomppi; Scott Geller; John G Flannery; William W Hauswirth; Eeva-Marja Sankila Journal: Eur J Hum Genet Date: 2010-08-18 Impact factor: 4.246
Authors: Maleeha Azam; Rob W J Collin; Muhammad Imran Khan; Syed Tahir Abbas Shah; Nadeem Qureshi; Muhammad Ajmal; Anneke I den Hollander; Raheel Qamar; Frans P M Cremers Journal: Mol Vis Date: 2009-09-05 Impact factor: 2.367
Authors: Nadia K Waheed; Ahmed H Qavi; Sarah N Malik; Maleeha Maria; Moeen Riaz; Frans P M Cremers; Maleeha Azam; Raheel Qamar Journal: Mol Vis Date: 2012-05-12 Impact factor: 2.367
Authors: James A Poulter; Molly S C Gravett; Rachel L Taylor; Kaoru Fujinami; Julie De Zaeytijd; James Bellingham; Atta Ur Rehman; Takaaki Hayashi; Mineo Kondo; Abdur Rehman; Muhammad Ansar; Dan Donnelly; Carmel Toomes; Manir Ali; Elfride De Baere; Bart P Leroy; Nigel P Davies; Robert H Henderson; Andrew R Webster; Carlo Rivolta; Christina Zeitz; Omar A Mahroo; Gavin Arno; Graeme C M Black; Martin McKibbin; Sarah A Harris; Kamron N Khan; Chris F Inglehearn Journal: Hum Mutat Date: 2020-11-30 Impact factor: 4.700