caa a22 4500 397574681 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/hmg/5.10.1533 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.10.1533 Treacher Collins Syndrome may Result from Insertions, Deletions or Splicing Mutations, Which Introduce a Termination Codon into the Gene [Elektronische Daten] [Amanda J. Gladwin, Jill Dixon, Stacie K. Loftus, Sara Edwards, John J. Wasmuth, Raoul C. M. Hennekam, Michael J. Dixon] Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Recently, the Treacher Collins syndrome gene (TCOF1) has been positionally cloned and a series of five mutations within the coding sequence of the gene identified. In the current investigation, seven exons of TCOF1 have been identified which has permitted the identification of additional mutations in the gene. The mutations that have been identified are three distinct deletions and an insertion, which cause a frameshift, and a missense mutation which inactivates a donor splice site with extension of transcription into the intron. To date, all 10 of the mutations which have been reported result in a premature termination codon and are unique to a given family. As these mutations are spread throughout the gene, these observations provide further support for the hypothesis that Treacher Collins syndrome results from haploinsufficiency, although a dominant negative effect cannot, at this stage, be excluded. © 1996 Oxford University Press Gladwin Amanda J. School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut Dixon Jill School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut Loftus Stacie K. Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92717, USA aut Edwards Sara School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut Wasmuth John J. Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92717, USA aut Hennekam Raoul C. M. Department of Pediatrics and Institute of Human Genetics, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands aut Dixon Michael J. School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut Human Molecular Genetics Oxford University Press 5/10(1996-10), 1533-1538 0964-6906 5:10<1533 1996 5 hmg https://doi.org/10.1093/hmg/5.10.1533 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.10.1533 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gladwin Amanda J. School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut NATIONALLICENCE 700 1- Dixon Jill School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut NATIONALLICENCE 700 1- Loftus Stacie K. Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92717, USA aut NATIONALLICENCE 700 1- Edwards Sara School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut NATIONALLICENCE 700 1- Wasmuth John J. Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92717, USA aut NATIONALLICENCE 700 1- Hennekam Raoul C. M. Department of Pediatrics and Institute of Human Genetics, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Dixon Michael J. School of Biological Sciences and Departments of Dental Medicine and Surgery, 3.239, Stopford Building University of Manchester, Oxford Road, Manchester M13 9PT, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/10(1996-10), 1533-1538 0964-6906 5:10<1533 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford