2. Academic Validation
  3. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

  • Nat Genet. 2012 Jan 22;44(3):338-42. doi: 10.1038/ng.1084.
Beverley H Anderson 1,  Paul R Kasher,  Josephine Mayer,  Marcin Szynkiewicz,  Emma M Jenkinson,  Sanjeev S Bhaskar,  Jill E Urquhart,  Sarah B Daly,  Jonathan E Dickerson,  James O'Sullivan,  Elisabeth Oppliger Leibundgut,  Joanne Muter,  Ghada M H Abdel-Salem,  Riyana Babul-Hirji,  Peter Baxter,  Andrea Berger,  Luisa Bonafé,  Janice E Brunstom-Hernandez,  Johannes A Buckard,  David Chitayat,  Wui K Chong,  Duccio M Cordelli,  Patrick Ferreira,  Joel Fluss,  Ewan H Forrest,  Emilio Franzoni,  Caterina Garone,  Simon R Hammans,  Gunnar Houge,  Imelda Hughes,  Sebastien Jacquemont,  Pierre-Yves Jeannet,  Rosalind J Jefferson,  Ram Kumar,  Georg Kutschke,  Staffan Lundberg,  Charles M Lourenço,  Ramesh Mehta,  Sakkubai Naidu,  Ken K Nischal,  Luís Nunes,  Katrin Ounap,  Michel Philippart,  Prab Prabhakar,  Sarah R Risen,  Raphael Schiffmann,  Calvin Soh,  John B P Stephenson,  Helen Stewart,  Jon Stone,  John L Tolmie,  Marjo S van der Knaap,  Jose P Vieira,  Catheline N Vilain,  Emma L Wakeling,  Vanessa Wermenbol,  Andrea Whitney,  Simon C Lovell,  Stefan Meyer,  John H Livingston,  Gabriela M Baerlocher,  Graeme C M Black,  Gillian I Rice,  Yanick J Crow
Affiliations

Affiliation

  • 1 Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, UK.
PMID: 22267198 DOI: 10.1038/ng.1084
Abstract

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only Enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

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