title: New best1 mutations in autosomal recessive bestrophinopathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *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.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Fung
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldberg
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Nissen
authors.forename: Alfonso
authors.initials: A
authors.lastname: Giovannini
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Merriam
authors.forename: Elena N
authors.initials: EN
authors.lastname: Bukanova
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cai
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Yannuzzi
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000328:Adult; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins