Splice site mutation in the peripherin/RDS gene associated with pattern dystrophy of the retina.
OBJECTIVE
To report the phenotype and genotype of a splice site mutation at intron 2 of the peripherin/RDS gene in four half-siblings with pattern dystrophy of the retina.


METHODS
Experimental study.


METHODS
In four siblings with a common mother and three separate fathers, complete ophthalmic examination, pedigree, electrophysiologic testing, and fluorescein angiography studies were obtained. Genomic DNA from serum lymphocytes was isolated and used as a template for primers specific for the cone homeobox gene (CRX), rhodopsin (RHO), and peripherin/RDS genes to conduct single stranded conformational analysis and cycle sequencing.


RESULTS
The pedigree of four affected siblings suggested probable autosomal dominance transmission of pattern dystrophy. In the four siblings, best corrected visual acuity ranged from 20/20 to 20/80 by Snellen chart. Clinical findings included discrete, localized degenerative changes of the macular retinal pigment epithelium in all patients, with subclassification foveal. One patient exhibited pigment clumping within the atrophic areas. Another patient exhibited yellow flecks diffusely in the macula. Fluorescein angiographic findings included central hypofluorescence with a surrounding rim of hyperfluorescence that corresponded to the observed fundus lesions and window defects. There was a range of electroretinography (ERG) and electrooculography (EOG) findings. One patient demonstrated both cone and rod dysfunction on ERG testing and another demonstrated decreased rod function. EOG testing was normal in two patients and mildly diminished in one patient. DNA sequencing identified a point mutation in intron 2 of the peripherin/RDS gene, consisting of an A to T change at 1068+3, present in all four affected patients.


CONCLUSIONS
Four siblings with pattern dystrophy of the retina presented a splice site mutation in the peripherin/RDS gene.
Sears
J E
JE
Cole Eye Institute, 9500 Euclid Avenue Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. searsj@ccf.org
Aaberg
T A
TA
Daiger
S P
SP
Moshfeghi
D M
DM
D000328:Adult; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007438:Introns; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D022821:RNA Splice Sites / Q000235:genetics*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D022821:RNA Splice Sites