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Kamron N Khan, Graham E Holder, Andrew Webster, Anthony G Robson, Anthony T Moore, Michel Michaelides; The fundus phenotype associated with the p.Ala243Val BEST1 mutation.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):654. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Best Disease (BD) is associated with a vitelliform maculopathy. We now present findings from a retrospective case series, which describe a unique and recognisable retinal phenotype, associated with a specific BEST1 mutation (p.Ala243Val), which differs from the classical phenotype.
Study PopulationPatients diagnosed with a macular dystrophy in the inherited retinal disease (IRD) clinics at Moorfields Eye Hospital, London, where genetic testing identified a specific, pathogenic BEST1 allele (p.Ala243Val). A control group of patients with BD (p.Arg218Cys) was also identified from an in-house inherited eye disease database.InvestigationPhenotypic and molecular characteristics are presented. These include: Slit lamp biomicroscopy, Colour fundus photography (CFP), Spectral-domain optical coherence tomography (SD-OCT), 488nm fundus autofluorescence (FAF), Visual Acuity (VA).
Group 1: p.Ala243Val BEST1Eight individuals were identified (six pedigrees). The mean age of symptom onset was 47 years (range 32-78 years). Typical vitelliform lesions were not apparent. SD-OCT revealed multifocal subretinal deposits at the macula. FAF imaging identified a reticular pattern of hyperautofluorescnce, similar to that observed with the “pattern dystrophies”. The electrooculogram (EOG) was recorded in five cases and in one case was near normal (170%/175%).Group 2: p.Arg218Cys BEST1Seven patients were identified. The mean age of symptom onset was 18 years (range 9-33 years), significantly lower than that observed in Group 1 (Student’s T-test, p=0.0002). In all cases typical vitelliform lesions were present, confirmed by SD-OCT. FAF showed that the vitelliform deposits were hyperautofluorescent as expected. The EOG was recorded in four patients, and abnormal in all.
The heterozygous BEST1 mutation p.Ala243Val appears to produce a unique and reproducible retinal phenotype, not observed with other pathogenic dominant alleles. When compared to the p.Arg218Cys variant, it appears to cause milder disease, with a later onset of symptoms, and possibly a milder reduction in EOG Arden ratio. Accordingly it may be mistaken for another dominantly inherited retinal dystrophy – PRPH2-related “pattern dystrophy”. The presence of subretinal fluid, identified by SD-OCT, may help differentiate the two.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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