title: Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy in Japanese Cohort.
abstract: OBJECTIVE
  To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB).
  
  
  METHODS
  Retrospective, multicenter observational case series.
  
  
  METHODS
  Nine ARB patients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed.
  
  
  RESULTS
  Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for Best vitelliform macular dystrophy were not seen in any of the patients. Seven patients shared some of the previously described features of ARB: subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other 2 patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in 2 patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8-year of follow-up period.
  
  
  CONCLUSIONS
  Japanese ARB patients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Nakanishi
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: ueno@med.nagoya-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kominami
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Gekka
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hirakata
authors.affiliation: Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Fujinami
authors.affiliation: Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008269:Macular Edema / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies; D058471:Subretinal Fluid / Q000378:metabolism; D014792:Visual Acuity; D055815:Young Adult
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins