title: A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism.
abstract: We have determined a molecular defect to be the likely basis for inactivity of the tyrosinase (EC 1.14.18.1) from a patient with tyrosinase-negative oculocutaneous albinism. A single base (thymine) was inserted in exon 5 of the tyrosinase gene following codon 471 in the putative transmembrane coding region. This insertion caused a shift in the reading frame of 19 amino acids at the 3' end and introduced a premature termination signal that would be expected to truncate the protein by 21 amino acids at the carboxyl terminus. The albino tyrosinase was not recognized by antibodies directed to the carboxyl terminus of tyrosinase. Furthermore, as shown by gel electrophoresis of the immunoprecipitated protein, the tyrosinase was approximately 3 kDa smaller than normal. Similar immunoprecipitation data were obtained when cloned normal and mutant tyrosinases were expressed in COS-1 cells.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202-5120.
authors.forename: C D
authors.initials: CD
authors.lastname: Chintamaneni
authors.forename: R
authors.initials: R
authors.lastname: Halaban
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: C J
authors.initials: CJ
authors.lastname: Witkop
authors.forename: B S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011233:Precipitin Tests; D012313:RNA / Q000032:analysis; D014162:Transfection
chemical_list: D004251:DNA Transposable Elements; D012313:RNA; D004247:DNA; D014442:Monophenol Monooxygenase