title: Phenotypic variability in RDH5 retinopathy (Fundus Albipunctatus).
abstract: OBJECTIVE
  To describe phenotypic variability and report novel mutational data in patients with mutation in RDH5 (fundus albipunctatus).
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Nine patients from 8 families (aged 7-55 years) with night blindness and electrophysiologic or fundoscopic findings in keeping with RDH5 mutation were ascertained.
  
  
  METHODS
  Detailed ophthalmologic examination, fundus photography, fundus autofluorescence imaging, spectral domain optical coherence tomography (SD-OCT), and electrophysiologic assessment were performed. The coding region and intron-exon boundaries of RDH5 were analyzed.
  
  
  METHODS
  RDH5 mutation status and resultant clinical and functional characteristics.
  
  
  RESULTS
  Eleven mutations in RDH5 were detected in the 8 families in the study, with 9 of these changes being novel. Visual acuity was normal in all but 1 eye of a patient with adult-onset central visual loss. Most patients had white dots extending into the mid-periphery on fundus examination, consistent with fundus albipunctatus, but 1 patient had normal fundi. Autofluorescence imaging revealed an association between the white dots and the hyperautofluorescent foci in younger subjects. The overall autofluorescence signal appeared low in all patients. The SD-OCT changes included deposits associated with the white dots that extended from Bruch's membrane to the external limiting membrane and focal loss of outer segments. Full-field electroretinogram (ERG) performed after standard dark adaptation showed moderate to severe generalized rod system dysfunction. Dim flash rod system ERGs were undetectable (N = 3) or subnormal (N = 6), but normalized after prolonged dark adaptation in 7 cases. Scotopic bright flash ERGs contained a reduced b:a ratio ("negative" ERG) in most cases; the use of a red stimulus under dark adaptation and extended recordings in the dark-adapted state in 1 patient identified dark-adapted cones as the probable source of the ERG signals. Photopic responses were abnormal in 6 of 9 cases.
  
  
  CONCLUSIONS
  The clinical and electrophysiologic phenotype of patients with RDH5 retinopathy is variable. Mutations in RDH5 lead to reduced autofluorescence signal possibly because of absence of retinoid-derived fluorophores. The dark-adapted bright flash ERG is often electronegative and likely a manifestation of the dark-adapted cone system exposed in the absence of normal rod function.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Moorfields Eye Hospital, London, United Kingdom; Institute of Ophthalmology, University College London, London, UK.
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sohn
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Vikki A
authors.initials: VA
authors.lastname: McBain
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Wright
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D000293:Adolescent; D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D000429:Alcohol Oxidoreductases; C105846:retinol dehydrogenase 5