title: Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism.
abstract: We have identified three different tyrosinase gene mutant alleles in four unrelated patients with type IB ("yellow") oculocutaneous albinism (OCA) and thus have demonstrated that type IB OCA is allelic to type IA (tyrosinase negative) OCA. In an inbred Amish kindred, type IB OCA results from homozygosity for a Pro----Leu substitution at codon 406. In the second family, type IB OCA results from compound heterozygosity for a type IA OCA allele (codon 81 Pro----Leu) and a novel type IB allele (codon 275 Val----Phe). In the third patient, type IB OCA results from compound heterozygosity for the same type IB allele (codon 275 Val----Phe) and a novel type IB OCA allele. In a fourth patient, type IB OCA results from compound heterozygosity for the codon 81 type IA OCA allele and a type IB allele that contains no identifiable abnormalities; dysfunction of this type IB allele apparently results from a mutation either well within one of the large introns or at some distance from the tyrosinase gene. In vitro expression of the Amish type IB allele in nonpigmented HeLa cells demonstrates that the Pro----Leu substitution at codon 406 greatly reduces but does not abolish tyrosinase enzymatic activity, a finding consistent with the clinical phenotype.
authors.affiliation: Department of Medical Genetics, University of Wisconsin, Madison 53706.
authors.forename: L B
authors.initials: LB
authors.lastname: Giebel
authors.forename: R K
authors.initials: RK
authors.lastname: Tripathi
authors.forename: K M
authors.initials: KM
authors.lastname: Strunk
authors.forename: J M
authors.initials: JM
authors.lastname: Hanifin
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: R A
authors.initials: RA
authors.lastname: King
authors.forename: R A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D006367:HeLa Cells; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014162:Transfection
chemical_list: D003062:Codon; D015345:Oligonucleotide Probes; D014442:Monophenol Monooxygenase