title: Course of visual decline in relation to the Best1 genotype in vitelliform macular dystrophy.
abstract: OBJECTIVE
  To describe the disease course in patients with vitelliform macular dystrophy (VMD) with a Best1 mutation and to determine the association between Best1 genotype and visual prognosis.
  
  
  METHODS
  Consecutive case series.
  
  
  METHODS
  Fifty-three patients with VMD with Best1 mutations from 27 Dutch families, aged 11 to 87 years.
  
  
  METHODS
  Best-corrected visual acuity (VA), fundus appearance, and Arden ratio on the electro-oculogram (EOG) during clinical follow-up were assessed from medical records. Mutation analysis of the Best1 gene was performed on DNA samples using denaturing high-pressure liquid chromatography and direct sequencing.
  
  
  METHODS
  Cumulative lifetime risk of visual decline below 0.5, 0.3, and 0.1 for the entire group and stratified for genotype.
  
  
  RESULTS
  Median age of onset of visual symptoms was 33 years (range: 2-78). The cumulative risk of VA below 0.5 (20/40) was 50% at 55 years and 75% at 66 years. The cumulative risk of decline less than 0.3 (20/63) was 50% by age 66 years and 75% by age 74 years. Two patients progressed to VA less than 0.1 (20/200). Fourteen different mutations were found. Most patients (96%) had missense mutations; the Thr6Pro, Ala10Val, and Tyr227Asn mutations were most common. Visual decline was significantly faster in patients with an Ala10Val mutation than either the Thr6Pro or the Tyr227Asn mutation (P=0.001).
  
  
  CONCLUSIONS
  Age of onset of visual symptoms varies greatly among patients with VMD. All patients show a gradual decrease in VA, and most progress to visual impairment at a relatively late age. Our data suggest a phenotype-genotype correlation, because the Ala10Val mutation has a more rapid disease progression than other common mutations.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Department of Clinical and Molecular Ophthalmogenetics, the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Booij
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: Jacoline B
authors.initials: JB
authors.lastname: ten Brink
authors.forename: Arne
authors.initials: A
authors.lastname: Bakker
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D014786:Vision Disorders / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology*
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins