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

被引：204

作者：

Anderson, Beverley H. ^{[1
]}

Kasher, Paul R. ^{[1
]}

Mayer, Josephine ^{[1
]}

Szynkiewicz, Marcin ^{[1
]}

Jenkinson, Emma M. ^{[1
]}

Bhaskar, Sanjeev S. ^{[1
]}

Urquhart, Jill E. ^{[1
]}

Daly, Sarah B. ^{[1
]}

Dickerson, Jonathan E. ^{[1
]}

O'Sullivan, James ^{[1
]}

Leibundgut, Elisabeth Oppliger ^{[2
,3
]}

Muter, Joanne ^{[4
]}

Abdel-Salem, Ghada M. H. ^{[5
]}

Babul-Hirji, Riyana ^{[6
]}

Baxter, Peter ^{[7
]}

Berger, Andrea ^{[8
,9
]}

Bonafe, Luisa ^{[10
]}

Brunstom-Hernandez, Janice E. ^{[11
]}

Buckard, Johannes A. ^{[12
]}

Chitayat, David ^{[6
,13
]}

Chong, Wui K. ^{[14
]}

Cordelli, Duccio M. ^{[15
]}

Ferreira, Patrick ^{[16
]}

Fluss, Joel ^{[17
]}

Forrest, Ewan H. ^{[18
]}

Franzoni, Emilio ^{[15
]}

Garone, Caterina ^{[15
,19
]}

Hammans, Simon R. ^{[20
]}

Houge, Gunnar ^{[21
]}

Hughes, Imelda ^{[22
]}

Jacquemont, Sebastien ^{[23
]}

Jeannet, Pierre-Yves ^{[24
]}

Jefferson, Rosalind J. ^{[25
]}

Kumar, Ram ^{[26
]}

Kutschke, Georg ^{[27
]}

Lundberg, Staffan ^{[28
]}

Lourenco, Charles M. ^{[29
]}

Mehta, Ramesh ^{[30
]}

Naidu, Sakkubai ^{[31
]}

Nischal, Ken K. ^{[32
,33
]}

Nunes, Luis ^{[34
]}

Ounap, Katrin ^{[35
]}

Philippart, Michel ^{[36
]}

Prabhakar, Prab ^{[37
]}

Risen, Sarah R. ^{[38
]}

Schiffmann, Raphael ^{[39
]}

Soh, Calvin ^{[40
]}

Stephenson, John B. P. ^{[41
]}

Stewart, Helen ^{[42
]}

Stone, Jon ^{[43
]}

机构：

[1] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[2] Univ Hosp Bern, Dept Clin Res, CH-3010 Bern, Switzerland

[3] Univ Bern, Bern, Switzerland

[4] Univ Manchester, Stem Cell & Leukaemia Prote Lab, Manchester, Lancs, England

[5] Natl Res Ctr, Human Genet & Genome Res Div, Dept Clin Genet, Cairo, Egypt

[6] Univ Toronto, Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada

[7] Sheffield Childrens Natl Hlth Serv NHS Fdn Trust, Ryegate Ctr, Sheffield, S Yorkshire, England

[8] Johannes Gutenberg Univ Mainz, Dept Pediat Neurol, Mainz, Germany

[9] Childrens Hosp Harlaching, Dept Pediat Neurol, Munich, Germany

[10] CHU Vaudois, Div Mol Pediat, CH-1011 Lausanne, Switzerland

[11] Washington Univ, Sch Med, Dept Neurol, St Louis Childrens Hosp, St Louis, MO 63110 USA

[12] Evangel Krankenhaus EVK Dusseldorf, Sozialpadiatr Zentrum, Dusseldorf, Germany

[13] Univ Toronto, Mt Sinai Hosp, Prenatal Diag & Med Genet Program, Dept Obstet & Gynecol, Toronto, ON M5G 1X5, Canada

[14] Great Ormond St Hosp Sick Children, Dept Radiol, London WC1N 3JH, England

[15] Univ Bologna, S Orsola Malpighi Hosp, Child Neuropsychiat Unit, Bologna, Italy

[16] Alberta Childrens Prov Gen Hosp, Div Med Genet, Calgary, AB, Canada

[17] Geneva Childrens Hosp, Geneva, Switzerland

[18] Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland

[19] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA

[20] Southampton Gen Hosp, Wessex Neurol Ctr, Southampton SO9 4XY, Hants, England

[21] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[22] Cent Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Manchester, Lancs, England

[23] CHU Vaudois, Serv Genet Med, CH-1011 Lausanne, Switzerland

[24] CHU Vaudois, Dept Pediat, Pediat Neurol Unit, CH-1011 Lausanne, Switzerland

[25] Royal Berkshire Hosp, Dingley Specialist Childrens Ctr, Reading RG1 5AN, Berks, England

[26] Alder Hey Childrens NHS Fdn Trust, Dept Neurol, Liverpool, Merseyside, England

[27] Univ Klinikum Saarlandes, Kliniken Kinder & Jugendmed, Klin Allgemeine Padiatrie & Neonatol, Homburg, Germany

[28] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden

[29] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Neurosci, Neurogenet Unit, Sao Paulo, Brazil

[30] Bedford Hosp NHS Trust, Bedford, England

[31] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Neurogenet Unit,Hugo Moser Res Inst, Baltimore, MD USA

[32] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA

[33] UPMC, Ctr Eye, Pittsburgh, PA USA

[34] Univ Nova Lisboa, Fac Ciencias Med, Dept Med Genet, Hosp Dona Estefania,Ctr Hosp Lisboa Cent CHLC, P-1200 Lisbon, Portugal

[35] Tartu Univ Hosp, United Labs, Dept Genet, Tartu, Estonia

[36] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA

[37] Great Ormond St Hosp Sick Children, Dept Neurol, London WC1N 3JH, England

[38] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD USA

[39] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA

[40] Salford Royal NHS Fdn Trust, Dept Neuroradiol, Salford, Lancs, England

[41] Royal Hosp Sick Children, Fraser Allander Neurosci Unit, Glasgow G3 8SJ, Lanark, Scotland

[42] Oxford Radcliffe Hosp NHS Trust, Dept Clin Genet, Oxford, England

[43] Western Gen Hosp, Dept Clin Neurosci, Edinburgh EH4 2XU, Midlothian, Scotland

[44] Royal Hosp Sick Children, Dept Clin Genet, Glasgow G3 8SJ, Lanark, Scotland

[45] Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, Amsterdam, Netherlands

[46] Ctr Hosp Lisboa Cent, Hosp Dona Estefania, Dept Neurol, Lisbon, Portugal

[47] Univ Libre Bruxelles, Ctr Human Genet, Dept Med Genet, Brussels, Belgium

[48] NW London Hosp NHS Trust, NW Thames Reg Genet Serv, Harrow, Middx, England

[49] Univ Libre Bruxelles, Hop Erasme, Dept Pediat Neurol, Brussels, Belgium

[50] Southampton Univ Hosp Fdn Trust, Southampton, Hants, England

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

关键词：

CEREBRORETINAL MICROANGIOPATHY; FAMILIAL SYNDROME; CALCIFICATIONS; PROTEIN; CYSTS; DNA; LEUKOENCEPHALOPATHY; DEFECTS; CST;

D O I：

10.1038/ng.1084

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha 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.

引用

页码：338 / U1604

页数：6

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