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A Novel BEST1 Mutation in Autosomal Recessive Bestrophinopathy

 Christopher Seungkyu Lee  ;  Ikhyun Jun  ;  Seung-il Choi  ;  Ji Hwan Lee  ;  Min Goo Lee  ;  Sung Chul Lee  ;  Eung Kweon Kim 
Journal Title
Issue Date
Aged ; Bestrophins ; Chloride Channels/genetics* ; Chloride Channels/metabolism ; DNA/genetics* ; DNA Mutational Analysis ; Electrooculography ; Electroretinography ; Eye Diseases, Hereditary/diagnosis ; Eye Diseases, Hereditary/genetics* ; Eye Diseases, Hereditary/metabolism ; Eye Proteins/genetics* ; Eye Proteins/metabolism ; Female ; Fluorescein Angiography ; Fundus Oculi ; Genes, Recessive ; Genetic Testing ; HEK293 Cells ; Humans ; Male ; Middle Aged ; Mutation* ; Pedigree ; Phenotype ; Retinal Diseases/diagnosis ; Retinal Diseases/genetics* ; Retinal Diseases/metabolism ; Retinal Pigment Epithelium/metabolism* ; Retinal Pigment Epithelium/pathology ; Retinal Pigment Epithelium/physiopathology ; Tomography, Optical Coherence
PURPOSE: 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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Corneal Dystrophy Research Institute (각막이상증연구소) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Sung Chul(이성철) ORCID logo https://orcid.org/0000-0001-9438-2385
Lee, Christopher Seungkyu(이승규) ORCID logo https://orcid.org/0000-0001-5054-9470
Lee, Ji Hwan(이지환)
Jun, Ik Hyun(전익현) ORCID logo https://orcid.org/0000-0002-2160-1679
Choi, Seung Il(최승일) ORCID logo https://orcid.org/0000-0001-7168-8795
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