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Fung, Adrian T. MMed*,‡‡,§§; Yzer, Suzanne MD, PhD*,†; Goldberg, Naomi MD*,‡; Wang, Hao MD; Nissen, Michael MD**; Giovannini, Alfonso MD††; Merriam, Joanna E. MD, PhD; Bukanova, Elena N. MD; Cai, Carolyn BA; Yannuzzi, Lawrence A. MD*,†; Tsang, Stephen H. MD, PhD†,§; Allikmets, Rando PhD†,§

doi: 10.1097/IAE.0000000000000387
Original Study

Purpose: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations.

Methods: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing.

Results: Five affected patients from four families were identified. Mean age was 16 years (range, 6–42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected.

Conclusion: Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy–associated dominant mutations.

The authors report genotypes and phenotypes of five patients from four families with autosomal recessive bestrophinopathy. The authors found novel deleterious BEST1 mutations. Carriers of autosomal recessive bestrophinopathy mutations have a normal phenotype.

*Vitreous-Retina-Macula Consultants of New York and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Institute, New York, New York;

Department of Ophthalmology, Columbia University, New York, New York;

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York;

§Department of Pathology and Cell Biology, Columbia University, New York, New York;

Albany Medical Center, Albany, New York;

**Department of Ophthalmology, Weill Cornell Medical College, New York, New York;

††Ophthalmology Section, Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy;

‡‡Australian School of Advanced Medicine, Macquarie University Hospital, Sydney, Australia; and

§§Save Sight Institute, University of Sydney, Sydney, Australia.

Reprint requests: Rando Allikmets, PhD, Eye Institute Research, Room 202, 160 Fort Washington Avenue, New York, NY 10032; e-mail:

Supported in part by the Macula Foundation, Inc by Stichting Wetenschappelijk Onderzoek Oogziekenhuis Rotterdam, Rotterdamse Blindenbelangen, Stichting Blindenhulp, Gelderse Blinden Stichting, Landelijke Stichting voor Blinden en Slechtzienden and grants from the National Eye Institute/NIH EY021163, EY019861, EY018213, EY019007 (Core Support for Vision Research), and unrestricted funds from Research to Prevent Blindness, New York, NY to the Department of Ophthalmology, Columbia University.

None of the authors have any financial/conflicting interests to disclose.

A. T. Fung and S. Yzer are co-first authors.

© 2015 by Ophthalmic Communications Society, Inc.