DOMINANT RETINITIS-PIGMENTOSA ASSOCIATED WITH 2 RHODOPSIN GENE-MUTATIONS - LEU-40-ARG AND AN INSERTION DISRUPTING THE 5'-SPLICE JUNCTION OF EXON-5

Objective: To determine the phenotypes of two families in which retinitis pigmentosa cosegregates with a rhodopsin (RHO) gene mutation: a leucine-to-arginine change at codon 40 (Leu-40-Arg) in one family, and a 150-base pair insertion that disrupts the RHO 5'-splice junction of exon 5 in another. Patients: Three affected members of each family. Results: The Leu-40-Arg mutation was associated with the onset of night blindness in the first decade of life. By the fourth decade, severe retinal functional loss was evident on dark-adapted static threshold perimetry, and electroretinographic responses were absent or barely detectable. In contrast, the RHO 150-base pair insertion was associated with the later onset of mild night vision difficulties; in two individuals, mild night vision difficulties were first noticed in the second decade while a third, a 25-year-old woman, was asymptomatic. Dark-adapted static threshold perimetry of this latter individual revealed a ''regional'' or class 2 pattern of retinal functional loss associated with equal loss of rod and cone electroretinographic responses. Conclusion: The RHO Leu-40-Arg mutation causes symptomatic retinal dysfunction by the end of the first decade while the insertion disrupting the 5'-splice junction of RHO exon 5 causes later onset ''regional' or class 2 retinal dysfunction.