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Kean T. Oh, MD; Richard G. Weleber, MD; Andrew Lotery, MD, FRCOphth; Dawn M. Oh, MS; Andrea M. Billingslea, BS; Edwin M. Stone, MD, PhD

Arch Ophthalmol. 2000;118:1269-1276.

Objectives  To report the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a proline-to-alanine mutation at codon 23 (Pro23Ala) of the rhodopsin gene and to compare this phenotype with that associated with the more common proline-to-histidine mutation at codon 23 (Pro23His).

Methods  We examined 6 patients within a single pedigree. The electroretinograms (ERGs) of 35 patients with known Pro23His mutations and of 22 healthy individuals were reviewed. Scotopic dim flash–response amplitudes, maximum combined-response amplitudes, and photopic-response amplitudes from the ERGs of these patients were plotted against age. The ERG indices of 5 individuals in the Pro23Ala family were compared with those of the patients with Pro23His mutations and of healthy individuals. Multiple linear regression was performed to evaluate the effect of age and mutation type on amplitudes. Mutation detection was performed using single-strand conformation polymorphism analysis, followed by automated DNA sequencing.

Results  Patients with the Pro23Ala mutation have a clinical phenotype characterized by onset of symptoms in the second to fourth decades of life, loss of superior visual field with relatively well-preserved inferior fields, and mild nyctalopia. Comparison with patients with the Pro23His mutation demonstrates statistically significant differences (P<.001) in responses to dim flash, maximum combined, and photopic responses between patients with these mutations after controlling for the effects of age. Patients with Pro23Ala mutations were less affected by ERG criteria than patients with Pro23His mutations. Patients with Pro23Ala mutations also differed significantly from healthy patients in all ERG indices examined (P<.001), after controlling for age.

Conclusion  We describe a rare mutation in codon 23 of rhodopsin causing autosomal dominant retinitis pigmentosa. The retinal dystrophy associated with the Pro23Ala mutation is characteristically mild in presentation and course, with greater preservation of ERG amplitudes than the more prevalent Pro23His mutation.

From the Department of Ophthalmology and Visual Science, University of Iowa Hospitals and Clinics, Iowa City (Drs Oh, Lotery, and Stone); and the Department of Ophthalmology, Casey Eye Institute (Dr Weleber and Ms Billingslea), and the Department of Molecular and Medical Genetics (Dr Weleber), Oregon Health Sciences University, Portland. Ms Oh is a freelance statistician in Iowa City.

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