Lack of autofluorescence in fundus albipunctatus associated with mutations in RDH5.
OBJECTIVE
The purpose of this study was to characterize the phenotype of fundus albipunctatus associated with RDH5 mutations.


METHODS
Four unrelated patients (patients 1-4) aged 35, 32, 19, and 8 years were examined with full-field electroretinography, multifocal electroretinography, optical coherence tomography, and fundus autofluorescence photography. Molecular genetic investigations included sequencing of RDH5 and RLBP1.


RESULTS
Patients 1 to 3 harbored homozygous mutations (c.881G>C, c.625C>T, and c.382G>A, respectively) and patient 4 harbored the compound heterozygous mutations (c.95delT and c.712G>T) in RDH5. A large variability in retinal dysfunction caused by RDH5 mutations was found but not fully explained by a simple prediction of reduced enzymatic function. All patients showed lack of autofluorescence of the fundus, indicating a reduced supply of 11-cis retinal to the photoreceptors. The lesions corresponding to the white dots did not autofluoresce and were seen on optical coherence tomography as discrete hyperreflective elements in the outer retina extending from the external limiting membrane to Bruch membrane.


CONCLUSIONS
Mutations in RDH5 associated with fundus albipunctatus seem to prevent normal lipofuscin accumulation. A relatively good functional status of 2 of 3 adult patients indicates that interference with 11-cis retinol dehydrogenase function may be a promising strategy for therapeutic intervention in retinal disorders featuring excessive lipofuscin accumulation.
Schatz
Patrik
P
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark. patrik.schatz@med.lu.se
Preising
Markus
M
Lorenz
Birgit
B
Sander
Birgit
B
Larsen
Michael
M
Eckstein
Christoph
C
Rosenberg
Thomas
T
D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005453:Fluorescence; D005654:Fundus Oculi; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D009154:Mutation; D010775:Photic Stimulation; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D055815:Young Adult
C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D008062:Lipofuscin; D000429:Alcohol Oxidoreductases; C105846:retinol dehydrogenase 5