title: Detection of a novel silent deletion, a missense mutation and a nonsense mutation in TCOF1.
abstract: BACKGROUND
  Treacher Collins syndrome (TCS) is a disorder of craniofacial development, that is caused by mutations in the TCOF1 gene. TCS is inherited as an autosomal dominant trait, and haploinsufficiency of the TCOF1 gene product treacle is proposed to be etiologically involved.
  
  
  METHODS
  Mutational analysis of the TCOF1 gene was done in 10 patients diagnosed with TCS using single-strand conformation polymorphism and direct sequencing.
  
  
  RESULTS
  Among these 10 patients, a novel 9 bp deletion was found, together with a previously reported 2 bp deletion, a novel missense mutation and a novel nonsense mutation in three different families. Familial studies allowed judgment of whether these abnormal findings were responsible for the TCS phenotype, or not. The 9 bp deletion of three amino acids Lys-Glu-Lys (1378-1380), which was located in the nuclear localization domain of treacle, seemed not essential for the treacle function. In contrast, the novel mutation of Ala26Val is considered to affect the LisH domain, an important domain of treacle. All of the mutations thus far detected in exon 5 have resulted in frameshift, but a nonsense mutation was detected (Lys159Stop).
  
  
  CONCLUSIONS
  The information obtained in the present study provides additional insights into the functional domains of treacle.
authors.affiliation: Research Group of Human Gene Therapy, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. hfujioka@med.hokudai.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fujioka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Katsumi
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishikiriyama
authors.forename: Kimie
authors.initials: K
authors.lastname: Oyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Tsuneki
authors.initials: T
authors.lastname: Sugihara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sakiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000409:Alanine; D018389:Codon, Nonsense; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008239:Lysine; D008342:Mandibulofacial Dysostosis / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014633:Valine
chemical_list: D018389:Codon, Nonsense; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human; D014633:Valine; D008239:Lysine; D000409:Alanine