Clinical findings in a multigeneration family with autosomal dominant central areolar choroidal dystrophy associated with an Arg195Leu mutation in the peripherin/RDS gene.
OBJECTIVE
To characterize clinical findings associated with a mutation in codon 195 (Arg195Leu) of the peripherin/RDS gene in a large multigeneration family of European decent.


METHODS
Sixteen members from 2 generations underwent ophthalmologic examination, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. All affected family members underwent Farnsworth Panel-D15 color testing. Five selected family members with early stages of the disease underwent multifocal electroretinography. Full-field electroretinography was performed in 2 family members with more advanced fundus changes. Finally, former patients' records and fundus images were analyzed to determine the course of the disease in affected individuals.


RESULTS
Nine family members in 2 generations were diagnosed as having autosomal dominant central areolar choroidal dystrophy. The family demonstrated an age-dependent increase of central granular fundus abnormalities with progressive development of geographic atrophy. Interindividual phenotypic variability was apparent and ranged from predominantly drusenlike depositions to single perifoveal pigment clumps. Age of onset of visual disturbances varied between 27 and 48 years. All individuals who manifested signs of disease were found to carry an Arg195Leu mutation in the peripherin/RDS gene.


CONCLUSIONS
Age of onset, progression of the disease, and characteristic fundus abnormalities share similarities to previous reports on families with central areolar choroidal dystrophy associated with peripherin/RDS gene mutations in codons 172, 142, and 195, respectively. However, striking variability in individual phenotypic findings and age of onset in our family suggests that additional factors that modify the defined peripherin/RDS gene mutation Arg195Leu likely influence the severity of the disease.


CONCLUSIONS
Caution should be advised in predicting the clinical course and severity of the disease based solely on a specific mutation in the peripherin/RDS gene.
Keilhauer
Claudia N
CN
Department of Ophthalmology, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany. ckeilhauer@yahoo.com
Meigen
Thomas
T
Weber
Bernhard H F
BH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001120:Arginine / Q000235:genetics; D015862:Choroid Diseases / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007930:Leucine / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D017354:Point Mutation; D014792:Visual Acuity
D003062:Codon; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D001120:Arginine; D007930:Leucine