Comparison of the clinical expression of retinitis pigmentosa associated with rhodopsin mutations at codon 347 and codon 23

Abstract

Purpose 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. Conclusion 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.