DEFECTS IN THE RHODOPSIN KINASE GENE IN THE OGUCHI FORM OF STATIONARYNIGHT BLINDNESS

Oguchi disease is a recessively inherited form of stationary night bli ndness due to malfunction of the rod photoreceptor mechanism. Patients with this disease show a distinctive golden-brown colour of the fundu s that occurs as the retina adapts to light, called the Mizuo phenomen on. Recently a defect in arrestin, a member of the rod phototransducti on pathway, was found to cause this disease in some Japanese patients( 1). 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 i n 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 mutatio ns in the rhodopsin kinase gene. Two cases were found to be homozygous for a deletion encompassing exon 5, predicted to lead to a nonfunctio nal protein. The third case was a compound heterozygote with two allel ic mutations, a missense mutation (Val380Asp) affecting a residue in t he catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resu lting in truncation of the carboxy terminus. Our results indicate that null mutations in the rhodopsin kinase gene are a cause of Oguchi dis ease and extend the known genetic heterogeneity in congenital stationa ry night blindness.