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Khan, Kamron, N., PhD, FRCOphth*,†,‡; Islam, Farrah, FCPS, FRCS; Moore, Anthony, T., FRCS, FRCOphth*,†,§; Michaelides, Michel, MD(Res), FRCOphth*,†

doi: 10.1097/IAE.0000000000001569
Original Study

Purpose: To describe a highly recognizable and reproducible retinal phenotype associated with a specific BEST1 mutation—p.Ala243Val.

Methods: Retrospective review of consecutive cases where genetic testing has identified p.Ala243Val BEST1 as the cause of disease. Electronic patient records were used to extract demographic, as well as functional and anatomical data. These data were compared with those observed with the most common BEST1 genotype, p.Arg218Cys.

Results: Eight individuals (six families) were identified with the p.Ala243Val BEST1 mutation and seven patients with the pathologic variant p.Arg218Cys. No patients with mutation of codon 243 knowingly had a family history of retinal disease, whereas all patients with the p.Arg218Cys variant did. The maculopathy was bilateral in all cases. The p.Ala243Val mutation was associated with a pattern dystrophy–type appearance, most visible with near-infrared reflectance and fundus autofluorescence imaging. This phenotype was never observed with any other genotype. This mutation was associated with an older median age of symptom onset (median = 42, interquartile range = 22) compared with those harboring the p.Arg218Cys mutation (median = 18, interquartile range = 12; Mann–Whitney U test; P < 0.05). Despite their older age, the final recorded acuity seemed to be better in the p.Ala243Val group (median = 0.55, interquartile range = 0.6475; median = 0.33, interquartile range = 0.358), although this did not reach statistical significance (Mann–Whitney U test; P > 0.05).

Conclusion: The mutation p.Ala243Val is associated with highly recognizable and reproducible pattern dystrophy–like phenotype. Patients develop symptoms at a later age and tend to have better preservation of electrooculogram amplitudes.

Best disease is diagnosed in the presence of a well-defined vitelliform-shaped macular lesion. This article describes a second, highly recognizable and reproducible retinal phenotype associated with a specific BEST1 mutation—p.Ala243Val.

*University College London Institute of Ophthalmology, University College London, London, Unite Kingdom;

Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom;

Department of Ophthalmology, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom; and

§Department of Ophthalmology, University of California San Francisco School of Medicine, San Francisco, California.

Reprint requests: Kamron N. Khan, PhD, FRCOphth, Leeds Institute of Molecular Medicine, Leeds, LS9 7TF United Kingdom; e-mail:

National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology (United Kingdom; K.N.K., A.R.W., A.T.M., M.M.), Fight For Sight (United Kingdom; M.M.), Moorfields Eye Hospital Special Trustees (United Kingdom; M.M.), the Foundation Fighting Blindness (FFB, USA; A.T.M., M.M.), Retinitis Pigmentosa Fighting Blindness (United Kingdom; A.T.M., M.M.), and the Wellcome Trust (099173/Z/12/Z; M.M.). M. Michaelides is supported by an FFB Career Development Award. This research has been funded/supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration.

None of the authors have any conflicting interests to disclose.

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the “Department of Health.”

© 2018 by Ophthalmic Communications Society, Inc.