Mutations in CTC1, Encoding Conserved Telomere Maintenance Component 1, Cause Coats Plus

• Author(s): Anderson, B ; Kasher, P ; Mayer, J ; Szynkiewicz, M ; Jenkinson, E ; Bhaskar, S ; Urquhart, J ; Daly, S ; Dickerson, J ; O'Sullivan, J ; Leibundgut, E ; Muter, J ; Abdel-Salem, G ; Babul-Hirji, R ; Baxter, P ; Berger, A ; Bonafé, L ; Brunstom-Hernandez, J ; Buckard, J ; Chitayat, D ; Chong, W ; Cordelli, D ; Ferreira, P ; Fluss, J ; Forrest, E ; Franzoni, E ; Garone, C ; Hammans, S ; Houge, G ; Hughes, I ; Jacquemont, S ; Jeannet, P ; Jefferson, R ; Kumar, R ; Kutschke, G ; Lundberg, S ; Lourenço, C ; Mehta, R ; Naidu, S ; Nischal, K ; Nunes, L ; Ounap, K ; Philippart, M ; Prabhakar, P ; Risen, S ; Schiffmann, R ; Soh, C ; Stephenson, J ; Stewart, H ; Stone, J ; Tolmie, J ; van der Knaap, M ; Vieira, JP ; Vilain, C ; Wakeling, E ; Wermenbol, V ; Whitney, A ; Lovell, S ; Meyer, S ; Livingston, J ; Baerlocher, G ; Black, G ; Rice, G ; Crow, Y
• Date: 2012
• Persistent ID: http://hdl.handle.net/10400.17/2516
• Origin: Repositório do Centro Hospitalar de Lisboa Central, EPE
• Subject(s): Abnormalities, Multiple; Base Sequence; Flow Cytometry; Genetic Predisposition to Disease; Histones; Molecular Sequence Data; Retinal Telangiectasis; Sequence Analysis, DNA; Telomere; Telomere-Binding Proteins; HDE NEU PED; HDE GEN
• Document Type: Journal article
• Language: English
• Contributor(s): Repositório da Unidade Local de Saúde São José

Description

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.