title: RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression.
abstract: OBJECTIVE
  Human blindness caused by mutation of visual cycle genes has been discussed as potentially treatable by retinoid replacement either through gene transfer or pharmacological bypass. Mutations in the RDH12 gene disrupt the visual cycle in vitro, but little is known of the in vivo effects of mutant RDH12, other than the association with severe early-onset autosomal recessive retinal disease. The relationship of retinal organization and visual function in patients with RDH12 mutations was determined and comparisons made with the disease from mutations in another visual cycle gene, RPE65.
  
  
  METHODS
  Young patients with RDH12 mutations were studied with optical coherence tomography (OCT) and colocalized measures of vision with dark-adapted absolute thresholds. Results were compared to those in patients with RPE65 mutations.
  
  
  RESULTS
  Retinal architecture of patients with RDH12 mutations was appreciably distorted, precluding identification of the normal laminae. Some RDH12-mutant retinas were remarkably thick and others were thin, but all had the same dysplastic pattern. A comparison with the structural and functional consequences in patients with mutations in RPE65 indicated that the pathogenesis of retinal degeneration in RDH12 mutations was distinctly different.
  
  
  CONCLUSIONS
  The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12.
authors.affiliation: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. jacobsos@mail.med.upenn.edu
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Elizabeth A M
authors.initials: EA
authors.lastname: Windsor
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Roman
authors.forename: Elise
authors.initials: E
authors.lastname: Heon
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Debra A
authors.initials: DA
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D001766:Blindness / Q000151:congenital*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D003623:Dark Adaptation; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011601:Psychophysics; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014785:Vision, Ocular; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D000429:Alcohol Oxidoreductases; D002352:Carrier Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C448939:CRB1 protein, human; C489649:RDH12 protein, human