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Elliott H. Sohn, MD; Peter J. Francis, MD, PhD; Jacque L. Duncan, MD; Richard G. Weleber, MD; David A. Saperstein, MD; Donald F. Farrell, MD; Edwin M. Stone, MD, PhD

Arch Ophthalmol. 2009;127(7):913-920.

Objective  To study the phenotypic characteristics of patients with a novel p.E292K mutation in BEST1.

Methods  Affected individuals underwent ophthalmic examination and testing that included photography, autofluorescence, optical coherence tomography, and electrophysiological testing. Their DNA was analyzed for BEST1 mutations.

Results  Five patients aged 5 to 59 years who expressed the p.E292K mutation in BEST1 were identified in 3 families. Electro-oculographic light-rise was subnormal in all probands and carriers. Carriers had normal findings from fundus examination, multifocal electroretinography, and visual acuity, and were emmetropic or myopic. Only probands had hyperopia and fundus findings typical of Best macular dystrophy. Optical coherence tomography of vitelliform lesions demonstrated retinal pigment epithelium elevation without subretinal fluid; atrophic lesions exhibited disruption of the hyperreflective outer retina–retinal pigment epithelium complex. Intense hyperautofluorescence correlated with the vitelliform lesion.

Conclusions  Patients with the Glu292Lys variation in BEST1 exhibit intrafamilial and interfamilial phenotypic variability. A disproportionate fraction (26%) of Best disease–causing mutations occurs in exon 8, suggesting that the portion of protein encoded by this exon (amino acids 290-316) may be especially important to bestrophin's function. Relatively good visual acuity with vitelliform lesions can be explained by preservation of the outer retina, demonstrated by optical coherence tomography.

Clinical Relevance  A novel mutation in this region of BEST1 carries implications for disease pathogenesis.

Author Affiliations: Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles (Dr Sohn); Departments of Ophthalmology (Drs Sohn) and Neurology (Dr Farrell), University of Washington, Seattle; Oregon Retinal Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland (Drs Francis and Weleber); Department of Ophthalmology, University of California San Francisco, San Francisco (Dr Duncan); Vitreoretinal Associates, Seattle (Dr Saperstein); Department of Ophthalmology and Visual Sciences and the Howard Hughes Medical Institute, University of Iowa, Iowa City (Dr Stone).

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