title: Tyrosinase gene (TYR) mutations in Chinese patients with oculocutaneous albinism type 1.
abstract: BACKGROUND
  To identify the sequence variants of the tyrosinase (TYR) gene in Chinese families with oculocutaneous albinism.
  
  
  METHODS
  Three families with oculocutaneous albinism type 1 and 95 unrelated healthy Chinese individuals with normal pigmentation were screened for mutations in the TYR gene by direct sequencing. Computational algorithms were used to characterize the biological significance of the mutants.
  
  
  RESULTS
  Four previously reported mutations (R299C, R299H, W400L and frame-shift c.930insC) and one novel mutation (F214del) were identified, and probands had homozygous or compound heterozygous TYR mutant alleles. None of the mutants were identified among the 95 normal control subjects. Computational analysis predicted that the R299C mutant inactivates the tyrosinase enzyme by misfolding of protein tertiary structure and/or retention of the misfolded tyrosinase within the endoplasmic reticulum, and F214del causes dysfunction of tyrosine enzyme by affecting the copper binding sites and altering substrate orientation and electronic transfers during catalytic reactions for melanosynthesis.
  
  
  CONCLUSIONS
  We have identified five different TYR mutations, including one novel mutation, which caused oculocutaneous albinism type 1 in Chinese. Further analysis of the patients will be useful to determine the effects of these mutations on the tyrosinase activities.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Kwong-Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Leo W L
authors.initials: LW
authors.lastname: Chan
authors.forename: Tak-Yeung
authors.initials: TY
authors.lastname: Leung
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Sylvia W Y
authors.initials: SW
authors.lastname: Chiang
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: D000328:Adult; D000368:Aged; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D014442:Monophenol Monooxygenase