title: Novel and homozygous BEST1 mutations in Chinese patients with Best vitelliform macular dystrophy.
abstract: OBJECTIVE
  The purpose of this study was to investigate the BEST1 gene mutations in Chinese patients with Best vitelliform macular dystrophy (BVMD).
  
  
  METHODS
  Twenty-six subjects from 7 Chinese families with BVMD and 100 unrelated healthy Chinese subjects without a family history of BVMD were screened for mutations in the BEST1 gene by direct sequencing. The subjects underwent complete ophthalmologic examination and BEST1 gene screening.
  
  
  RESULTS
  Six novel missense mutations (Thr2Asn, Leu75Phe, Ser144Asn, Arg255Trp, Pro297Thr, and Asp301Gly) and 1 previously reported mutation (Arg218Cys) were identified. Each family was found to have a unique BEST1 mutation that segregated with the disease. Two of the six novel mutations are located within the four previously reported common mutation clusters within the BEST1 gene. One family with patients having homozygous Leu75Phe mutations did not have the more severe BVMD phenotype. None of the patients with mutations was identified among the 100 healthy control subjects.
  
  
  CONCLUSIONS
  A large number of unique novel missense mutations was found in Chinese patients with BVMD, suggesting considerable interethnic differences between the mutation sites in the BEST1 gene in different populations. The few truncating BEST1 mutations and the lack of a more severe phenotype in homozygous patients suggest that the missense BEST1 mutation may produce a dominant negative effect on wild-type BEST1 gene.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Raymond L M
authors.initials: RL
authors.lastname: Wong
authors.forename: Ping
authors.initials: P
authors.lastname: Hou
authors.forename: Kwong-Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Sylvia W Y
authors.initials: SW
authors.lastname: Chiang
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006720:Homozygote; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D008062:Lipofuscin