title: TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region.
abstract: Treacher Collins Syndrome (TCS) is the most common of the human mandibulofacial dysostosis disorders. Recently, a partial TCOF1 cDNA was identified and shown to contain mutations in TCS families. Here we present the entire exon/intron genomic structure and the complete coding sequence of TCOF1. TCOF1 encodes a low complexity protein of 1,411 amino acids, whose predicted protein structure reveals repeated motifs that mirror the organization of its exons. These motifs are shared with nucleolar trafficking proteins in other species and are predicted to be highly phosphorylated by casein kinase. Consistent with this, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localization signals. Throughout the open reading frame, we detected an additional eight mutations in TCS families and several polymorphisms. We postulate that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.
authors.affiliation: Department of Otorhinolaryngology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Wise
authors.forename: L C
authors.initials: LC
authors.lastname: Chiang
authors.forename: W A
authors.initials: WA
authors.lastname: Paznekas
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: M M
authors.initials: MM
authors.lastname: Musy
authors.forename: J A
authors.initials: JA
authors.lastname: Ashley
authors.forename: M
authors.initials: M
authors.lastname: Lovett
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D018076:DNA, Complementary; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human