title: Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients.
abstract: OBJECTIVE
  To report 11 cases of autosomal recessive vitelliform macular dystrophy and to compare their molecular findings and phenotypic characteristics with those of patients with the more common and well-described dominant form of the disease.
  
  
  METHODS
  Blood samples were obtained from 435 unrelated individuals with a clinical diagnosis of vitelliform macular dystrophy and screened for mutations in the coding sequences of BEST1. Medical records and retinal photographs of selected patients were reviewed.
  
  
  RESULTS
  Nine of the 435 probands were found to have 2 plausible disease-causing variations in BEST1, while 198 individuals were found to have heterozygous variations compatible with autosomal dominant inheritance. Inheritance phase was determined in three of the recessive families. Six novel disease-causing mutations were identified among these recessive patients: Arg47Cys, IVS7-2A>G, IVS7+4G>A, Ile205del12ATCCTGCTCCAGAG, Pro274Arg, and Ile366delCAGGTGTGGC. Forty-four novel disease-causing mutations were identified among the patients with presumed autosomal dominant disease. The phenotype of patients with recessive alleles for BEST1 ranged from typical vitelliform lesions to extensive extramacular deposits.
  
  
  CONCLUSIONS
  The authors provide evidence that two abnormal BEST1 alleles, neither of which causes macular disease alone, can act in concert to cause early-onset vitelliform macular dystrophy.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Carver Family Center for Macular Degeneration, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Tyson R
authors.initials: TR
authors.lastname: Kinnick
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dev
authors.forename: Monique
authors.initials: M
authors.lastname: Leys
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Christine N
authors.initials: CN
authors.lastname: Kay
authors.forename: Byron L
authors.initials: BL
authors.lastname: Lam
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Elias
authors.initials: E
authors.lastname: Traboulsi
authors.forename: Raymond
authors.initials: R
authors.lastname: Iezzi
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D012189:Retrospective Studies; D014792:Visual Acuity / Q000502:physiology; D057826:Vitelliform Macular Dystrophy / Q000175:diagnosis / Q000235:genetics*
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins