• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (33)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Macular Degeneration  • Alert me on articles by topic  Social Bookmarking   What's this?

Clinicopathologic Correlation

Robert F. Mullins, PhD; Kean T. Oh, MD; Edward Heffron, MA; Gregory S. Hageman, PhD; Edwin M. Stone, MD, PhD

Arch Ophthalmol. 2005;123:1588-1594.

Objective  To provide the clinicopathologic findings of a patient who developed the clinical characteristics of Best disease (typically considered a juvenile macular degeneration) at the age of 75 years after being documented to be ophthalmoscopically normal at the age of 51 years.

Design  A member of a large family with Best disease, possessing a Y227N mutation in the VMD2 gene (the gene responsible for the disease, which encodes the bestrophin protein), developed small vitelliform lesions in both eyes at the age of 75 years and later developed yellow flecklike depositions at the level of the retinal pigment epithelium (RPE), which were also identified in fundus photographs of family members. The patient died at the age of 93 years, and the histological features of the macular lesion and peripheral flecks were examined.

Results  Histopathologically, the retinal outer nuclear layer was attenuated, particularly in the macula. This attenuation was frequently associated with normal RPE. A large area of photoreceptor degeneration was present in the central macula, with loss of the underlying RPE cells. Outside of this region, the RPE density was within normal limits. The peripheral flecks were clusters of basal laminar deposits and drusen. Bestrophin immunohistochemistry revealed labeling along both the basolateral and apical membranes of the RPE.

Conclusions  Findings characteristic of Best disease may not manifest in a molecularly affected individual until late in life. Mutations in bestrophin appear to lead to extracellular deposit formation outside the macula in some families. The distribution of bestrophin in the RPE suggests that the protein may be mistargeted in those with Best disease who have the Y227N mutation, and that this may be a cause of the associated RPE and photoreceptor dysfunction.

Author Affiliations: Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City (Drs Mullins, Hageman, and Stone and Mr Heffron); Retina Eye Center, Augusta, Ga (Dr Oh); and Howard Hughes Medical Institute, Chevy Chase, Md (Dr Stone). Dr Oh is now with Retinal Consultants of Arizona, Phoenix.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Three-dimensional Distribution of the Vitelliform Lesion, Photoreceptors, and Retinal Pigment Epithelium in the Macula of Patients With Best Vitelliform Macular Dystrophy
Kay et al.
Arch Ophthalmol 2011;0:archophthalmol.2011.363v1-8.
ABSTRACT | FULL TEXT  

Disease-associated missense mutations in bestrophin-1 affect cellular trafficking and anion conductance
Milenkovic et al.
J. Cell Sci. 2011;124:2988-2996.
ABSTRACT | FULL TEXT  

The Spectrum of Subclinical Best Vitelliform Macular Dystrophy in Subjects with Mutations in BEST1 Gene
Querques et al.
IOVS 2011;52:4678-4684.
ABSTRACT | FULL TEXT  

Molecular Consequences of BEST1 Gene Mutations in Canine Multifocal Retinopathy Predict Functional Implications for Human Bestrophinopathies
Guziewicz et al.
IOVS 2011;52:4497-4505.
ABSTRACT | FULL TEXT  

Evaluation of Macular Structure and Function by OCT and Electrophysiology in Patients with Vitelliform Macular Dystrophy Due to Mutations in BEST1
Schatz et al.
IOVS 2010;51:4754-4765.
ABSTRACT | FULL TEXT  

Suppression of Ca2+ signaling in a mouse model of Best disease
Zhang et al.
Hum Mol Genet 2010;19:1108-1118.
ABSTRACT | FULL TEXT  

Phenotypic Variability Due to a Novel Glu292Lys Variation in Exon 8 of the BEST1 Gene Causing Best Macular Dystrophy
Sohn et al.
Arch Ophthalmol 2009;127:913-920.
ABSTRACT | FULL TEXT  

Retinal Function in Best Macular Dystrophy: Relationship between Electrophysiological, Psychophysical, and Structural Measures of Damage
Maia-Lopes et al.
IOVS 2008;49:5553-5560.
ABSTRACT | FULL TEXT  

Clinical and Genetic Heterogeneity in Multifocal Vitelliform Dystrophy
Boon et al.
Arch Ophthalmol 2007;125:1100-1106.
ABSTRACT | FULL TEXT  

Differential Macular and Peripheral Expression of Bestrophin in Human Eyes and Its Implication for Best Disease
Mullins et al.
IOVS 2007;48:3372-3380.
ABSTRACT | FULL TEXT  

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model for Best Disease
Guziewicz et al.
IOVS 2007;48:1959-1967.
ABSTRACT | FULL TEXT  

New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy
Marchant et al.
J. Med. Genet. 2007;44:e70-e70.
ABSTRACT | FULL TEXT  

The Bestrophin Mutation A243V, Linked to Adult-Onset Vitelliform Macular Dystrophy, Impairs Its Chloride Channel Function
Yu et al.
IOVS 2006;47:4956-4961.
ABSTRACT | FULL TEXT  

The Light Peak of the Electroretinogram Is Dependent on Voltage-gated Calcium Channels and Antagonized by Bestrophin (Best-1)
Marmorstein et al.
JGP 2006;127:577-589.
ABSTRACT | FULL TEXT