title: Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.
abstract: OBJECTIVE
  To assess the allelic variation of the VMD2 gene in patients with Best disease and age-related macular degeneration (AMD).
  
  
  METHODS
  Three hundred twenty-one AMD patients, 192 ethnically similar control subjects, 39 unrelated probands with familial Best disease, and 57 unrelated probands with the ophthalmoscopic findings of Best disease but no family history were screened for sequence variations in the VMD2 gene by single-strand conformation polymorphism (SSCP) analysis. Amplimers showing a bandshift were reamplified and sequenced bidirectionally. In addition, the coding regions of the VMD2 gene were completely sequenced in six probands with familial Best disease who showed no SSCP shift.
  
  
  RESULTS
  Forty different probable or possible disease-causing mutations were found in one or more Best disease or AMD patients. Twenty-nine of these variations are novel. Of the 39 probands with familial Best disease, mutations were detected in all 39 (33 by SSCP and 6 by DNA sequencing). SSCP screening of the 57 probands with a clinical diagnosis of Best disease but no family history revealed 16 with mutations. Mutations were found in 5 of 321 AMD patients (1.5%), a fraction that was not significantly greater than in control individuals (0/192, 0%).
  
  
  CONCLUSIONS
  Patients with the clinical diagnosis of Best disease are significantly more likely to have a mutation in the VMD2 gene if they also have a positive family history. These findings suggest that a small fraction of patients with the clinical diagnosis of AMD may actually have a late-onset variant of Best disease, whereas at the same time, a considerable fraction of isolated patients with the ophthalmoscopic features of Best disease are probably affected with some other macular disease.
authors.affiliation: Department of Ophthalmology, The University of Iowa College of Medicine, Iowa City 52242, USA. edwin-stone@uiowa.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Lotery
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.forename: G A
authors.initials: GA
authors.lastname: Fishman
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: L M
authors.initials: LM
authors.lastname: Affatigato
authors.forename: B E
authors.initials: BE
authors.lastname: Nichols
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D017931:DNA Primers; D005136:Eye Proteins