RDS gene mutations causing retinitis pigmentosa or macular degeneration lead to the same abnormality in photoreceptor function.
OBJECTIVE
To investigate functional abnormalities in mutations in the peripherin (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 167 (Gly167Asp) leading to macular degeneration and another with a mutation in codon 210 (Pro210Ser) leading to retinitis pigmentosa, were studied with clinical examinations and measurements of rod and cone sensitivities and dark adaptation, electroretinography, and rhodopsin levels.


RESULTS
Mildly affected patients had sizable rod and cone electroretinograms, reduced levels of rhodopsin, and minor losses of sensitivity. In both mutations, there were delays of rod and cone dark adaptation after bleaching, and the adaptational abnormalities were observed in peripheral and central retinal locations. Analysis of the kinetics of rod adaptation indicates that the underlying abnormalities are similar in both mutations and that the effects of the mutations are similar to those caused by mild systemic vitamin A deficiency.


CONCLUSIONS
Patients with the Gly167Asp and Pro210Ser mutations in the peripherin/RDS gene have widely different clinical phenotypes but show the same abnormality, slowed dark adaptation, of rod and cone photoreceptor function. The similarities of the characteristics of the adaptational abnormalities in the two genotypes suggest that, in addition to the structural roles normally assumed for it, peripherin influences or participates in the function of the visual cycle.
Kemp
C M
CM
Department of Ophthalmology, University of Miami School of Medicine, Bascom Palmer Eye Institute, FL 33136.
Jacobson
S G
SG
Cideciyan
A V
AV
Kimura
A E
AE
Sheffield
V C
VC
Stone
E M
EM
D000293:Adolescent; D000328:Adult; D003623:Dark Adaptation; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins; D064531:Peripherins; D010786:Photoreceptor Cells / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D014794:Visual Fields
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D012243:Rhodopsin