title: Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull's-eye maculopathy.
abstract: OBJECTIVE
  To study the presence of Best macular dystrophy (VMD2) gene mutations in patients diagnosed with maculopathies other than classic Best disease and to describe the clinical characteristics of these subjects.
  
  
  METHODS
  Case-comparison study of phenotype-genotype correlations.
  
  
  METHODS
  Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic Best disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made.
  
  
  METHODS
  Presence of mutations in the Best gene (VMD2; OMIM 153700) and the clinical phenotype.
  
  
  RESULTS
  Three of 259 patients (1%) with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216I), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull's-eye maculopathy (variant in exon 4; E119Q), and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in exon 4; A146K).
  
  
  CONCLUSIONS
  Novel mutations in the VMD2 gene were found in patients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. Johanna_Seddon@meei.harvard.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Seddon
authors.forename: M A
authors.initials: MA
authors.lastname: Afshari
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: P S
authors.initials: PS
authors.lastname: Bernstein
authors.forename: S
authors.initials: S
authors.lastname: Chong
authors.forename: A
authors.initials: A
authors.lastname: Hutchinson
authors.forename: K
authors.initials: K
authors.lastname: Petrukhin
authors.forename: R
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D000368:Aged; D000075002:Bestrophins; D018118:Chloride Channels; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014792:Visual Acuity
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins