title: Ocular phenotype analysis of a family with biallelic mutations in the BEST1 gene.
abstract: OBJECTIVE
  To investigate the genetic cause and perform a comprehensive clinical analysis of a Danish family with autosomal recessive bestrophinopathy; to investigate whether Bestrophin may be expressed in normal human retina.
  
  
  METHODS
  Retrospective clinical and molecular genetic analysis and immunohistochemical observational study.
  
  
  METHODS
  setting: National referral center. participants: A family with 5 individuals and biallelic BEST1 mutations, and enucleated eyes from 2 individuals with nonaffected retinas. observation procedures: Molecular genetic analysis included sequencing of BEST1 and co-segregation analysis. Clinical investigations included electro-oculography, full-field electroretinography, multifocal electroretinography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging. Immunohistochemical analysis was performed. main outcome measures: BEST1 mutations, imaging findings, electroretinography amplitudes, and implicit times.
  
  
  RESULTS
  The index case was compound heterozygous for p.A195V and a novel 15 base pair deletion leading to p.Q238L. The index case at age 10 demonstrated multifocal vitelliform changes that were hyperautofluorescent, cystoid macular edema in the inner nuclear layer, no light rise in the electro-oculography, and a reduced central but preserved peripheral retinal function by multifocal electroretinography. Full-field electroretinography demonstrated a reduced rod response and inner retina dysfunction. Retinal structure was normal in all 3 family members who carried a sequence change in BEST1. Electro-oculography light peak was reduced in both the mother and sister (heterozygous for p.Q238L). Immunohistochemistry could not confirm the presence of Bestrophin in normal human retina.
  
  
  CONCLUSIONS
  Because of a relatively well preserved retinal function, autosomal recessive bestrophinopathy may be a suitable first candidate, among the BEST1-related ocular conditions, for gene replacement therapy.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark; National Eye Clinic, Kennedy Center, Glostrup, Denmark.
authors.forename: Sermed
authors.initials: S
authors.lastname: Al-Hamdani
authors.affiliation: Department of Ophthalmology, Clinical Sciences, Scane County University Hospital, University of Lund, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Engelsberg
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Liliana
authors.initials: L
authors.lastname: Mizrahi-Meissonnier
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Alexey
authors.initials: A
authors.lastname: Obolensky
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sander
authors.affiliation: National Eye Clinic, Kennedy Center, Glostrup, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark; National Eye Clinic, Kennedy Center, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark; National Eye Clinic, Kennedy Center, Glostrup, Denmark; Department of Ophthalmology, Clinical Sciences, Scane County University Hospital, University of Lund, Sweden. Electronic address: patrik.schatz@med.lu.se.
authors.forename: Patrik
authors.initials: P
authors.lastname: Schatz
mesh_terms: D000328:Adult; D000483:Alleles; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004585:Electrooculography; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000503:physiopathology; D012164:Retinal Diseases / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins