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 pati ents affected with autosomal-dominant transmitted retinitis pigmentosa (adRP) from a large Italian pedigree in which a point mutation predic ting the Arg-135-Trp change of rhodopsin was identified by polymerase chain reaction-single-strand conformation polymorphism analysis. Metho ds: Seven patients, ranging in age from 6 to 41 years, underwent a ful l clinical ophthalmologic evaluation, kinetic visual field testing, an d electroretinographic testing. Results: In agreement with previous re ports, this rhodopsin mutation yielded a particularly severe phenotype , both clinically and functionally. The evaluation of patients from th is pedigree in the first and second decade of life demonstrated that r etinal function is still electroretinographically measurable at least until 18 years of age, although reduced to 2% to 4% of normal. Longitu dinal measures showed that the rate of progression of the disease was unusually high, with an average 50% loss per year of electroretinograp hic amplitude and visual field area with respect to baseline. Later in the course of the disease, macular function is also severely compromi sed, 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 feature s make the Arg-135-Trp phenotype substantially different from the gene ral RP population, and also from many of the other adRP pedigrees with known rhodopsin mutations reported to date.