PMID- 10369264
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20141120
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Jun
TI  - Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark
      adaptation and fundus albipunctatus.
PG  - 188-91
AB  - 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 Muller 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.
FAU - Yamamoto, H
AU  - Yamamoto H
AD  - Berman-Gund Laboratory for the Study of Retinal Degenerations and the Ocular
      Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye & Ear
      Infirmary, Boston, USA.
FAU - Simon, A
AU  - Simon A
FAU - Eriksson, U
AU  - Eriksson U
FAU - Harris, E
AU  - Harris E
FAU - Berson, E L
AU  - Berson EL
FAU - Dryja, T P
AU  - Dryja TP
LA  - eng
SI  - GENBANK/AF037062
SI  - GENBANK/U43559
GR  - EY00169/EY/NEI NIH HHS/United States
GR  - EY08683/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase)
SB  - IM
MH  - Adaptation, Ocular/*genetics
MH  - Adolescent
MH  - Alcohol Oxidoreductases/*genetics
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Eye Diseases, Hereditary/enzymology/*genetics
MH  - Female
MH  - Fundus Oculi
MH  - Humans
MH  - In Vitro Techniques
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - *Point Mutation
MH  - Reference Values
MH  - Retinal Degeneration/enzymology/*genetics
MH  - Retinitis Pigmentosa/enzymology/genetics
EDAT- 1999/06/16 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/16 10:00
PHST- 1999/06/16 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/16 10:00 [entrez]
AID - 10.1038/9707 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jun;22(2):188-91. doi: 10.1038/9707.