title: THE FUNDUS PHENOTYPE ASSOCIATED WITH THE p.Ala243Val BEST1 MUTATION.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Kamron N
authors.initials: KN
authors.lastname: Khan
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Farrah
authors.initials: F
authors.lastname: Islam
authors.affiliation: University College London Institute of Ophthalmology, University College London, London, Unite Kingdom.|Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.|Department of Ophthalmology, University of California San Francisco School of Medicine, San Francisco, California.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: University College London Institute of Ophthalmology, University College London, London, Unite Kingdom.|Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
mesh_terms: D000328:Adult; D000368:Aged; D000075002:Bestrophins / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D057826:Vitelliform Macular Dystrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins