Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy.
OBJECTIVE
To evaluate the clinical and electrophysiologic findings in a family with two heterozygous sequence changes in the peripherin-retinal degeneration slow (RDS) gene.


METHODS
A family study was done of a pedigree obtained by screening for rhodopsin, peripherin/RDS, or rom-1 gene mutations in probands from families with hereditary retinal diseases. The patients consisted of three affected and four unaffected members from a family with cone dystrophy. Ophthalmoscopy, visual field testing, electroretinography, and DNA analysis were performed.


RESULTS
Denaturing gradient gel electrophoresis showed the presence of two different sequence changes in the RDS genes of this family. In three members with a retinal disease, the authors observed the substitution of phenylalanine for serine in codon 27 (serine-27-phenylalanine). The clinical and functional findings in these three patients were most consistent with autosomal-dominant cone dystrophy. Three other family members, unaffected with retinal disease, were found to show a substitution of serine for cysteine in codon 72 of the peripherin protein.


CONCLUSIONS
A peripherin/RDS sequence change may produce a cone dystrophy with minimal ophthalmoscopic changes in the macula and limited peripheral degenerative changes. Caution is warranted to avoid ascribing nondisease-causing sequence polymorphisms in candidate genes as responsible for determining the development of a retinal disease phenotype.
Fishman
G A
GA
Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago College of Medicine 60612, USA.
Stone
E M
EM
Alexander
K R
KR
Gilbert
L D
LD
Derlacki
D J
DJ
Butler
N S
NS
D000328:Adult; D000368:Aged; D004247:DNA / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005654:Fundus Oculi; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010375:Pedigree; D064531:Peripherins; D010649:Phenylalanine / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017421:Sequence Analysis; D012694:Serine / Q000235:genetics*; 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; D012694:Serine; D010649:Phenylalanine; D004247:DNA