title: Tyrosinase gene analysis in Japanese patients with oculocutaneous albinism.
abstract: BACKGROUND
  Oculocutaneous albinism (OCA) is a heterogeneous congenital disorder. Tyrosinase is a key enzyme in melanin biosynthesis, and tyrosinase gene mutations cause the OCA1 subtype.
  
  
  OBJECTIVE
  This study was intended evaluate the frequency and details of tyrosinase gene mutations in Japanese OCA patients.
  
  
  METHODS
  We examined nine non-consanguineous OCA families, sequenced the tyrosinase gene of the patients and also confirmed a splicing site mutation using exon trapping system.
  
  
  RESULTS
  Tyrosinase gene mutations were identified in five out of nine OCA families (55%). IVS2-10deltt-7t-a was present in 3 out of 18 alleles in three families (16%), P310insC was present in three alleles in three families (16%) and R278X was found in three alleles (16%), including those in one heterozygous and one compound homozygous patient. G97V (290 G-T) was found in 1 out of 18 alleles, and we could not find G97V in the mutation database. We have added this mutation as 9th mutation of Japanese OCA1 patients. In 8 of 18 alleles, four families, no tyrosinase mutations were identified. They were presumed not to be OCA1, but other subtypes of OCA. Exon trapping system demonstrated IVS2-10deltt-7t-a mutation generated the abnormal splicing site, and inserted the codon 4 bases in mRNA level resulting in premature termination codon downstream.
  
  
  CONCLUSIONS
  This study provided new information about OCA1 mutations, and highlights the requirement of broader detailed search to make precise diagnosis of OCA.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15, W 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Goto
authors.forename: Kazuko C
authors.initials: KC
authors.lastname: Sato-Matsumura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokota
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000293:Adolescent; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D002648:Child; D030541:Databases, Genetic; D005127:Eye Color / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D014442:Monophenol Monooxygenase