title: A Novel BEST1 Mutation in Autosomal Recessive Bestrophinopathy.
abstract: OBJECTIVE
  To describe the clinical characteristics associated with a newly identified mutant of autosomal recessive bestrophinopathy (ARB) and confirm the associated physiological functional defects.
  
  
  METHODS
  Two patients with ARB from one family underwent a full ophthalmic examination, including dilated fundus examination, fundus photography, fluorescein angiography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (OCT), electroretinography (ERG), and electrooculography (EOG). Subsequently, genetic analysis for bestrophin-1 (BEST1) mutations was conducted through direct Sanger sequencing. The effect of ARB-associated mutations of BEST1 on the cellular localization was determined by in vitro experiments. Whole-cell patch clamping was conducted to measure the chloride conductance of wild-type BEST1 and the identified BEST1 mutants in transfected HEK293T cells.
  
  
  RESULTS
  Two related patients (66-year-old brother and 52-year-old sister) presented with reduced visual acuity and bilateral symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole. Spectral-domain OCT showed macular thinning with submacular fluid. The female patient had a concomitant macular edema associated with branched retinal vein occlusion in the left eye, which responded well to intravitreal bevacizumab injections. Genetic analysis demonstrated that both patients were compound heterozygous for one novel (Leu40Pro) and one previously identified (Ala195Val) BEST1 variant. HEK293T cells transfected with the identified BEST1 mutant showed significantly small currents compared to those transfected with the wild-type gene, whereas cells cotransfected with mutant and wild-type BEST1 showed good chloride conductance. Cellular localization of BEST1 was well conserved to the plasma membrane in the mutants.
  
  
  CONCLUSIONS
  We have identified and described the phenotype and in vitro functional aspects of a new BEST1 mutation causing ARB. Clinically suspected ARB cases warrant genetic confirmation to confirm the diagnosis.
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Christopher Seungkyu
authors.initials: CS
authors.lastname: Lee
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea 3Brain Korea 21 PLUS Project for Medical Sciences, Severanc.
authors.forename: Ikhyun
authors.initials: I
authors.lastname: Jun
authors.affiliation: Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Choi
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea 3Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea 3Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Kor.
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
mesh_terms: D000368:Aged; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005808:Genes, Recessive; D005820:Genetic Testing; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D041623:Tomography, Optical Coherence
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D004247:DNA