title: Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness.
abstract: Oguchi disease is a recessively inherited form of stationary night blindness due to malfunction of the rod photoreceptor mechanism. Patients with this disease show a distinctive golden-brown colour of the fundus that occurs as the retina adapts to light, called the Mizuo phenomenon. Recently a defect in arrestin, a member of the rod phototransduction pathway, was found to cause this disease in some Japanese patients. As rhodopsin kinase works with arrestin in shutting off rhodopsin after it has been activated by a photon of light, it is reasonable to propose that some cases of Oguchi disease might be caused by defects in rhodopsin kinase. This report describes an analysis of the arrestin and rhodopsin kinase genes in three unrelated cases of Oguchi disease. No defects in arrestin were detected, but all three cases had mutations in the rhodopsin kinase gene. Two cases were found to be homozygous for a deletion encompassing exon 5, predicted to lead to a nonfunctional protein. The third case was a compound heterozygote with two allelic mutations, a missense mutation (Val380Asp) affecting a residue in the catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resulting in truncation of the carboxy terminus. Our results indicate that null mutations in the rhodopsin kinase gene are a cause of Oguchi disease and extend the known genetic heterogeneity in congenital stationary night blindness.
authors.affiliation: Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: K C
authors.initials: KC
authors.lastname: Sippel
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000483:Alleles; D019393:Arrestin / Q000502:physiology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000502:physiology; D051606:G-Protein-Coupled Receptor Kinase 1; D005808:Genes, Recessive; D006801:Humans; D008969:Molecular Sequence Data; D009755:Night Blindness / Q000145:classification / Q000151:congenital / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion
chemical_list: D019393:Arrestin; D005136:Eye Proteins; D011494:Protein Kinases; D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human