title: Novel insertion in exon 5 of the TCOF1 gene in twin sisters with Treacher Collins syndrome.
abstract: Treacher Collins syndrome (TCS) is associated with an abnormal differentiation of the first and second pharyngeal arches during fetal development. This causes mostly craniofacial deformities, which require numerous corrective surgeries. TCS is an autosomal dominant disorder and it occurs in the general population at a frequency of 1 in 50,000 live births. The syndrome is caused by mutations in the TCOF1 gene, which encodes the serine/alanine-rich protein named Treacle. Over 120 mutations of the TCOF1 gene responsible for TCS have been described. About 70% of recognized mutations are deletions, which lead to a frame shift, formation of a termination codon, and shortening of the protein product of the gene. Herewith, a new heterozygotic insertion, c.484_668ins185bp, was described in two monozygotic twin sisters suffering from TCS. This mutation was absent in their father, brother, and uncle, indicating a de novo origin. The insertion causes a shift in the reading frame and premature termination of translation at 167 aa. The novel insertion is the longest ever found in the TCOF1 gene and the only one found among monozygotic twin sisters.
authors.affiliation: Department of Genetics, Wrocław University of Environmental and Life Sciences, ul. Kożuchowska 7, 51-631 Wrocław, Poland. bozena.kruk@up.wroc.pl
authors.forename: Bożena Anna
authors.initials: BA
authors.lastname: Marszałek-Kruk
authors.forename: Piotr
authors.initials: P
authors.lastname: Wójcicki
authors.forename: Robert
authors.initials: R
authors.lastname: Smigiel
authors.forename: Wiesław H
authors.initials: WH
authors.lastname: Trzeciak
mesh_terms: D000293:Adolescent; D004247:DNA / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008342:Mandibulofacial Dysostosis / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D014427:Twins / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human; D004247:DNA