RDS GENE-MUTATIONS CAUSING RETINITIS-PIGMENTOSA OR MACULAR DEGENERATION LEAD TO THE SAME ABNORMALITY IN PHOTORECEPTOR FUNCTION

Purpose. To investigate functional abnormalities in mutations in the p eripherin (RDS) gene leading to different clinical types of autosomal dominant retinal disease-macular degeneration and retinitis pigmentosa . Methods. Patients from two families, one with a mutation in codon 16 7 (Gly167Asp) leading to macular degeneration and another with a mutat ion in codon 210 (Pro210Ser) leading to retinitis pigmentosa, were stu died with clinical examinations and measurements of rod and cone sensi tivities and dark adaptation, electroretinography, and rhodopsin level s. Results. Mildly affected patients had sizable rod and cone electror etinograms, reduced levels of rhodopsin, and minor losses of sensitivi ty. In both mutations, there were delays of rod and cone dark adaptati on after bleaching, and the adaptational abnormalities were observed i n peripheral and central retinal locations. Analysis of the kinetics o f rod adaptation indicates that the underlying abnormalities are simil ar in both mutations and that the effects of the mutations are similar to those caused by mild systemic vitamin A deficiency. Conclusions. P atients with the Gly167Asp and Pro210Ser mutations in the peripherin/R DS gene have widely different clinical phenotypes but show the same ab normality, slowed dark adaptation, of rod and cone photoreceptor funct ion. The similarities of the characteristics of the adaptational abnor malities in the two genotypes suggest that, in addition to the structu ral roles normally assumed for it, peripherin influences or participat es in the function of the visual cycle.