title: Molecular bases of tyrosinase-negative oculocutaneous albinism: a single base insertion or a missense point mutation in the tyrosinase gene.
abstract: We have identified two different mutations in the tyrosinase genes of Japanese patients with tyrosinase-negative oculocutaneous albinism (OCA). One is a single base insertion in the exon 2 of the tyrosinase gene that shifts the reading frame and introduces a premature termination codon (TGA) after the amino acid residue 298 (codon 316). The other is a G to A transition at residue 312, leading to a single amino acid substitution, arginine at position 59 (codon 77) to glutamine. The promoter activity of the patients' tyrosinase genes was evaluated in the cell-free transcription system prepared from pigmented melanoma cells, indicating that the patients' genes were accurately transcribed in vitro. It is therefore conceivable that the tyrosinase gene is expressed in their melanocytes. Furthermore, transient expression of the mutated genes indicates that the truncated tyrosinase or the tyrosinase containing glutamine 59 is unable to form melanin in melanocytes. We therefore propose that these mutations in the tyrosinase genes lead to a phenotype of tyrosinase-negative OCA.
authors.affiliation: Department of Dermatology, Thoku University School of Medicine, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: J
authors.initials: J
authors.lastname: Matsunaga
authors.forename: S
authors.initials: S
authors.lastname: Okinaga
authors.forename: S
authors.initials: S
authors.lastname: Shibahara
authors.forename: H
authors.initials: H
authors.lastname: Tagami
mesh_terms: D016115:Albinism, Oculocutaneous / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005796:Genes; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D014442:Monophenol Monooxygenase