Autosomal-dominant retinitis pigmentosa associated with an Arg-135-Trp point mutation of the rhodopsin gene. Clinical features and longitudinal observations.

PURPOSE: To report the clinical and functional characteristics of patients affected with autosomal-dominant transmitted retinitis pigmentosa (adRP) from a large Italian pedigree in which a point mutation predicting the Arg-135-Trp change of rhodopsin was identified by polymerase chain reaction-single-strand conformation polymorphism analysis.

METHODS

Seven patients, ranging in age from 6 to 41 years, underwent a full clinical ophthalmologic evaluation, kinetic visual field testing, and electroretinographic testing.

RESULTS

In agreement with previous reports, this rhodopsin mutation yielded a particularly severe phenotype, both clinically and functionally. The evaluation of patients from this pedigree in the first and second decade of life demonstrated that retinal function is still electroretinographically measurable at least until 18 years of age, although reduced to 2% to 4% of normal. Longitudinal measures showed that the rate of progression of the disease was unusually high, with an average 50% loss per year of electroretinographic amplitude and visual field area with respect to baseline. Later in the course of the disease, macular function is also severely compromised, leaving only residual central vision by the fourth decade of life.

CONCLUSIONS

The phenotype associated with mutations in codon 135 of the rhodopsin molecule appears to have an unusually high progression rate and yields an extremely poor prognosis. These distinctive features make the Arg-135-Trp phenotype substantially different from the general RP population, and also from many of the other adRP pedigrees with known rhodopsin mutations reported to date.