title: Novel mutations of TCOF1 gene in European patients with Treacher Collins syndrome.
abstract: BACKGROUND
  Treacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases.
  
  
  METHODS
  In this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication.
  
  
  RESULTS
  Fifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein.
  
  
  CONCLUSIONS
  This study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein.
authors.affiliation: Fondazione Policlinico di Tor Vergata, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Conte
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: D'Apice
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gambardella
authors.forename: Federica
authors.initials: F
authors.lastname: Sangiuolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D001483:Base Sequence; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005060:Europe; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000175:diagnosis / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human