A novel mutation in the RDS/Peripherin gene causes adult-onset foveomacular dystrophy.
OBJECTIVE
To describe a novel mutation in the RDS/Peripherin gene that results in a moderately severe form of adult-onset foveomacular dystrophy.


METHODS
Observational case series.


METHODS
Selected members of a family with adult-onset foveomacular dystrophy underwent complete ophthalmic evaluation, including fundus photography and fluorescein angiography, in a tertiary care referral center. The study population consisted of 12 members of a Caucasian kindred. After providing informed consent, patients donated blood for genomic DNA extraction and mutational screening using standard techniques. The main outcome measure were the presence of a RDS/Peripherin gene mutation in a patient with the disease and its absence in unaffected family members and controls.


RESULTS
Eight affected family members and no unaffected family members demonstrated a single guanine base deletion at nucleotide 112 that led to premature termination at amino acid 38 of RDS/Peripherin polypeptide. This frameshift mutation results in truncation of nearly 90% of the gene product, thus probably representing a null allele. That results in a relatively severe phenotype, with choroidal neovascularization developing in two patients and geographic atrophy involving the macula in three patients.


CONCLUSIONS
We describe a frameshift null mutation in the RDS/Peripherin gene associated with a relatively severe manifestation of adult-onset foveomacular dystrophy in affected family members.
Yang
Zhenglin
Z
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Lin
Wei
W
Moshfeghi
Darius M
DM
Thirumalaichary
Sukanya
S
Li
Xi
X
Jiang
Li
L
Zhang
Heidi
H
Zhang
Sheng
S
Kaiser
Peter K
PK
Traboulsi
Elias I
EI
Zhang
Kang
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000032:analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D017384:Sequence Deletion
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D004247:DNA