A peculiar autosomal dominant macular dystrophy caused by an asparagine deletion at codon 169 in the peripherin/RDS gene.
OBJECTIVE
To describe the clinical and genetic findings in a family with a peculiar autosomal dominant macular dystrophy with peripheral deposits.


METHODS
All family members underwent an ophthalmic examination, and their genomic DNA was screened for mutations in the human retinal degeneration slow (peripherin/RDS) and rhodopsin genes. In selected cases, fluorescein angiography and electrophysiologic testing were performed.


RESULTS
The age at onset of the disease was between the third and fourth decades of life, starting with mild visual acuity loss and periods of metamorphopsia. Clinical signs included subretinal yellowish macular deposits evolving into geographic atrophy and retinal hypopigmentation and hyperpigmentation. Electroretinography demonstrated rod dysfunction, and electro-oculograms were mildly to severely disturbed. All affected members were found to carry a 3-base pair deletion affecting codon 169 of the peripherin/RDS gene. This mutation resulted in an asparagine (Asn) deletion in the peripherin/RDS protein and was not found in 155 control individuals.


CONCLUSIONS
A deletion of Asn169 in the peripherin/RDS protein causes a peculiar form of autosomal dominant macular dystrophy in a large family from the Netherlands.


CONCLUSIONS
Characterizing the phenotype and genotype in this family may, in the long term, result in a better understanding of the precise mechanism underlying this retinal degeneration.
van Lith-Verhoeven
Janneke J C
JJ
Department of Ophthalmology, University Medical Center Nijmegen, The Netherlands.
van den Helm
Bellinda
B
Deutman
August F
AF
Bergen
Arthur A B
AA
Cremers
Frans P M
FP
Hoyng
Carel B
CB
de Jong
Paulus T V M
PT
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D016133:Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; 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; D001216:Asparagine; D012243:Rhodopsin