title: Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.
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.
authors.affiliation: Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, UK.
authors.forename: Beverley H
authors.initials: BH
authors.lastname: Anderson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kasher
authors.forename: Josephine
authors.initials: J
authors.lastname: Mayer
authors.forename: Marcin
authors.initials: M
authors.lastname: Szynkiewicz
authors.forename: Emma M
authors.initials: EM
authors.lastname: Jenkinson
authors.forename: Sanjeev S
authors.initials: SS
authors.lastname: Bhaskar
authors.forename: Jill E
authors.initials: JE
authors.lastname: Urquhart
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Daly
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Dickerson
authors.forename: James
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: Elisabeth Oppliger
authors.initials: EO
authors.lastname: Leibundgut
authors.forename: Joanne
authors.initials: J
authors.lastname: Muter
authors.forename: Ghada M H
authors.initials: GM
authors.lastname: Abdel-Salem
authors.forename: Riyana
authors.initials: R
authors.lastname: Babul-Hirji
authors.forename: Peter
authors.initials: P
authors.lastname: Baxter
authors.forename: Andrea
authors.initials: A
authors.lastname: Berger
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafé
authors.forename: Janice E
authors.initials: JE
authors.lastname: Brunstom-Hernandez
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Buckard
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Wui K
authors.initials: WK
authors.lastname: Chong
authors.forename: Duccio M
authors.initials: DM
authors.lastname: Cordelli
authors.forename: Patrick
authors.initials: P
authors.lastname: Ferreira
authors.forename: Joel
authors.initials: J
authors.lastname: Fluss
authors.forename: Ewan H
authors.initials: EH
authors.lastname: Forrest
authors.forename: Emilio
authors.initials: E
authors.lastname: Franzoni
authors.forename: Caterina
authors.initials: C
authors.lastname: Garone
authors.forename: Simon R
authors.initials: SR
authors.lastname: Hammans
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
authors.forename: Imelda
authors.initials: I
authors.lastname: Hughes
authors.forename: Sebastien
authors.initials: S
authors.lastname: Jacquemont
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Jeannet
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Jefferson
authors.forename: Ram
authors.initials: R
authors.lastname: Kumar
authors.forename: Georg
authors.initials: G
authors.lastname: Kutschke
authors.forename: Staffan
authors.initials: S
authors.lastname: Lundberg
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mehta
authors.forename: Sakkubai
authors.initials: S
authors.lastname: Naidu
authors.forename: Ken K
authors.initials: KK
authors.lastname: Nischal
authors.forename: Luís
authors.initials: L
authors.lastname: Nunes
authors.forename: Katrin
authors.initials: K
authors.lastname: Ounap
authors.forename: Michel
authors.initials: M
authors.lastname: Philippart
authors.forename: Prab
authors.initials: P
authors.lastname: Prabhakar
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Risen
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Calvin
authors.initials: C
authors.lastname: Soh
authors.forename: John B P
authors.initials: JB
authors.lastname: Stephenson
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Jon
authors.initials: J
authors.lastname: Stone
authors.forename: John L
authors.initials: JL
authors.lastname: Tolmie
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: Jose P
authors.initials: JP
authors.lastname: Vieira
authors.forename: Catheline N
authors.initials: CN
authors.lastname: Vilain
authors.forename: Emma L
authors.initials: EL
authors.lastname: Wakeling
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wermenbol
authors.forename: Andrea
authors.initials: A
authors.lastname: Whitney
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.forename: John H
authors.initials: JH
authors.lastname: Livingston
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001483:Base Sequence; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D058456:Retinal Telangiectasis / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods; D016615:Telomere / Q000473:pathology*; D034501:Telomere-Binding Proteins / Q000235:genetics*
chemical_list: C544945:Ctc1 protein, human; C468783:H2AX protein, human; D006657:Histones; D034501:Telomere-Binding Proteins