Macular dystrophy associated with the Arg172Trp substitution in peripherin/RDS: genotype-phenotype correlation.
OBJECTIVE
To document the evolution of geographic atrophy in the peripherin/RDS Arg172Trp substitution, provide age-related estimates of visual acuity, and compare with other missense mutations with a similar phenotype (Arg142Trp, Arg172Gln, and Arg195Leu).


METHODS
Total area of geographic atrophy in 18 affected individuals with the peripherin/RDS Arg172Trp substitution was measured from retinal photographs and plotted as a function of age. Visual acuity data from these individuals were collated with previously published cases of Arg172Trp substitution to obtain age-related estimates of visual acuity. These were compared with published series with the Arg142Trp, Arg172Gln, and Arg195Leu substitutions, using linear regression.


RESULTS
In patients with the Arg172Trp substitution, the increase in total area of chorioretinal atrophy and decline in visual acuity showed significant association with age (R2 = 0.619, P < 0.001; R2 = 0.761, P < 0.001). A trend was observed toward earlier age at onset and worse visual acuity with the Arg172Trp substitution as compared with the Arg142Trp and Arg172Gln substitutions. Linear regression analysis showed that until the age of 60 years, at any given age, visual acuity with the Arg172Trp substitution was significantly worse than the Arg142Trp (P < 0.001) and the Arg172Gln substitutions (P = 0.04). Patients above the age of 60 years were excluded as a floor effect on visual acuity was observed with visual acuity being worse than 6/60 for most patients.


CONCLUSIONS
This paper demonstrates that visual prognosis in macular dystrophies associated with peripherin/RDS may be mutation specific and, for the Arg172Trp substitution, worse than the Arg142Trp and Arg172Gln substitutions.
Anand
Seema
S
Department of Ophthalmology, St James's University Hospital, Leeds, United Kingdom.
Sheridan
Eamonn
E
Cassidy
Frances
F
Inglehearn
Chris
C
Williams
Grange
G
Springell
Kelly
K
Allgar
Victoria
V
Kelly
Thu-Lan
TL
McKibbin
Martin
M
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins