Lack of autofluorescence in fundus albipunctatus associated with mutations in RDH5

TY - JOUR

T1 - Lack of autofluorescence in fundus albipunctatus associated with mutations in RDH5

AU - Schatz, Patrik

AU - Preising, Markus

AU - Lorenz, Birgit

AU - Sander, Birgit

AU - Larsen, Michael

AU - Eckstein, Christoph

AU - Rosenberg, Thomas

PY - 2010/11

Y1 - 2010/11

N2 - Purpose: 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. Conclusion: 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.

AB - Purpose: 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. Conclusion: 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.

U2 - http://dx.doi.org/10.1097/IAE.0b013e3181dc050a

DO - http://dx.doi.org/10.1097/IAE.0b013e3181dc050a

M3 - Journal article

SN - 0275-004X

VL - 30

SP - 1704

EP - 1713

JO - Retina

JF - Retina

IS - 10

ER -