title: Comparison of the clinical expression of retinitis pigmentosa associated with rhodopsin mutations at codon 347 and codon 23.
abstract: OBJECTIVE
  To examine the difference in expression of retinitis pigmentosa from mutations at codon 23 and codon 347 or rhodopsin; to report a novel mutation in rhodopsin.
  
  
  METHODS
  Goldmann perimetry (solid angle of I4e isopter) and electroretinographic amplitudes (square root transform of a response ratio) were analyzed for 24 patients with mutations at codon 347 (15 with Pro347Ala, 2 with Pro347Gln, 6 with Pro347Leu, and 1 with a novel Pro347Cys change) and 41 patients with mutations at codon 23 (6 with Pro23Ala; 35 with Pro23His).
  
  
  RESULTS
  When all patients with mutations at codons 347 and 23 were compared, loss of visual fields was significantly worse in patients with codon 347 changes (P =.0003). Only rod responses of the electroretinograms were significantly different between the two groups (P =.048). Specific comparison of Pro347Ala with Pro23Ala using regression analysis demonstrated significant differences in severity between codon 23 and codon 347 patients for b-wave amplitudes of rod (P =.0069), cone (P =.039) and maximum combined response (P =.049). The solid angle of the I4e isopter was also significantly different (P =.025) between the groups after controlling for age. Modeling age by group for Pro347Ala comparison produced an R(2) of.44.
  
  
  CONCLUSIONS
  We reconfirmed that rhodopsin-related retinitis pigmentosa from mutations involving codon 347 produces a more severe phenotype than that involving codon 23. Accurate modeling of disease was shown to be possible by incorporating the effects of a patient's age and specific genotype. Therefore, both of these variables must be considered in prognostic counseling and subject recruitment for future therapeutic trials.
authors.affiliation: Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Kean T
authors.initials: KT
authors.lastname: Oh
authors.forename: Reid
authors.initials: R
authors.lastname: Longmuir
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Oh
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Kelly
authors.initials: K
authors.lastname: Kopp
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Brown
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Peter
authors.initials: P
authors.lastname: Sonkin
authors.forename: Karen M
authors.initials: KM
authors.lastname: Gehrs
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D003062:Codon; D012243:Rhodopsin