title: Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus.
abstract: The metabolic pathways that produce 11-cis retinal are important for vision because this retinoid is the chromophore residing in rhodopsin and the cone opsins. The all-trans retinal that is generated after cone and rod photopigments absorb photons of light is recycled back to 11-cis retinal by the retinal pigment epithelium and Müller cells of the retina. Several of the enzymes involved have recently been purified and molecularly cloned; here we focus on 11-cis retinol dehydrogenase (encoded by the gene RDH5; chromosome 12q13-14; ref. 4), the first cloned enzyme in this pathway. This microsomal enzyme is abundant in the retinal pigment epithelium, where it has been proposed to catalyse the conversion of 11-cis retinol to 11-cis retinal. We evaluated patients with hereditary retinal diseases featuring subretinal spots (retinitis punctata albescens and fundus albipunctatus) and patients with typical dominant or recessive retinitis pigmentosa for mutations in RDH5. Mutations were found only in two unrelated patients, both with fundus albipunctatus; they segregated with disease in the respective families. Recombinant mutant 11-cis retinol dehydrogenases had reduced activity compared with recombinant enzyme with wild-type sequence. Our results suggest that mutant alleles in RDH5 are a cause of fundus albipunctatus, a rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments.
authors.affiliation: Berman-Gund Laboratory for the Study of Retinal Degenerations and the Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Simon
authors.forename: U
authors.initials: U
authors.lastname: Eriksson
authors.forename: E
authors.initials: E
authors.lastname: Harris
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000221:Adaptation, Ocular / Q000235:genetics*; D000293:Adolescent; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D015785:Eye Diseases, Hereditary / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D012016:Reference Values; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics
chemical_list: D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase