title: Mutational analysis of the TCOF1 gene in 11 Japanese patients with Treacher Collins Syndrome and mechanism of mutagenesis.
abstract: Treacher Collins Syndrome (TCS) (OMIM 154500) is a congenital, craniofacial disorder inherited as an autosomal dominant trait. The responsible gene for TCS, TCOF1, was mapped to 5q32-33.1 and identified in 1996. Since then, TCOF1 mutations in patients with TCS have been reported from Europe, North and South America, however, no TCS cases from an Asian country have been molecularly characterized. Here we report mutational analysis for 11 Japanese patients with TCS for the first time, and have identified TCOF1 mutations in 9 of them. The mutations detected were various, but most likely all the mutations are predicted to result in a truncated gene product, known as treacle. One mutation frequently reported was included in our cases, but no missense mutations were detected. These findings are similar to those for the previous studies for TCS in other races. We have speculated about the molecular mechanisms of the mutations in most cases. Collectively, we have defined some of the characteristic molecular features commonly observed in TCS patients, irrespective of racial difference.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fujioka
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Igawa
authors.forename: Tsuneki
authors.initials: T
authors.lastname: Sugihara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sakiyama
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000235:genetics* / Q000473:pathology; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human; D004247:DNA