title: A homozygous frameshift mutation in BEST1 causes the classical form of Best disease in an autosomal recessive mode.
abstract: OBJECTIVE
  Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode.
  
  
  METHODS
  Clinical evaluation included detailed family history, a full ophthalmologic examination, electro-oculography (EOG), electroretinography, color vision testing, and ocular imaging. Mutation analysis was performed by direct sequencing of PCR products.
  
  
  RESULTS
  Two young siblings affected by Best disease, as confirmed by funduscopy, retinal imaging, and electrophysiologic assessment, were recruited for the study. Molecular analysis revealed a novel homozygous deletion (c.1415delT) in the BEST1 gene leading to a frameshift followed by a premature stop codon, which cosegregated with the disease in a recessive mode. The heterozygous parents had normal visual acuity, retinal appearance, and function. The two heterozygous grandmothers, ages 61 and 62, also had normal Arden ratios on EOG, but one of them manifested moderate-to-severe dry non-neovascular age-related macular degeneration.
  
  
  CONCLUSIONS
  We show here that the typical vitelliform phenotype of Best disease, usually transmitted in an autosomal dominant fashion, can be inherited as an autosomal recessive disease due to homozygosity for a frameshift mutation.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Bitner
authors.forename: Liliana
authors.initials: L
authors.lastname: Mizrahi-Meissonnier
authors.forename: Gabriel
authors.initials: G
authors.lastname: Griefner
authors.forename: Inbar
authors.initials: I
authors.lastname: Erdinest
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004585:Electrooculography; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D057826:Vitelliform Macular Dystrophy / Q000175:diagnosis / Q000235:genetics*
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins