Letter abstract
Nature Genetics 41, 829 - 832 (2009)
Published online: 14 June 2009 | doi:10.1038/ng.373
Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response
Gillian I Rice1,2, Jacquelyn Bond2, Aruna Asipu2, Rebecca L Brunette3, Iain W Manfield4, Ian M Carr2, Jonathan C Fuller4, Richard M Jackson4, Teresa Lamb5, Tracy A Briggs2, Manir Ali2, Hannah Gornall1, Lydia R Couthard2, Alec Aeby6, Simon P Attard-Montalto7, Enrico Bertini8, Christine Bodemer9, Knut Brockmann10, Louise A Brueton11, Peter C Corry12, Isabelle Desguerre13, Elisa Fazzi14, Angels Garcia Cazorla15, Blanca Gener16, Ben C J Hamel17, Arvid Heiberg18, Matthew Hunter19, Marjo S van der Knaap20, Ram Kumar21, Lieven Lagae22, Pierre G Landrieu23, Charles M Lourenco24, Daphna Marom25, Michael F McDermott2, William van der Merwe26, Simona Orcesi14, Julie S Prendiville27, Magnhild Rasmussen28, Stavit A Shalev29, Doriette M Soler7, Marwan Shinawi30, Ronen Spiegel29, Tiong Y Tan31, Adeline Vanderver32, Emma L Wakeling33, Evangeline Wassmer34, Elizabeth Whittaker35, Pierre Lebon36, Daniel B Stetson3, David T Bonthron2 & Yanick J Crow1
Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.
- Academic Unit of Medical Genetics, University of Manchester, Manchester, UK.
- Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds, UK.
- Department of Immunology, University of Washington, Seattle, USA.
- JIF Centre for Biomolecular Interactions, Astbury Centre for Structural Molecular Biology, Manton Building, University of Leeds, Leeds, UK.
- DNA Laboratory, Yorkshire Regional Genetics Service, Ashley Wing, St. James's University Hospital, Leeds, UK.
- Department of Paediatric Neurology, Erasme Hospital-ULB, Brussels, Belgium.
- Department of Paediatrics, The Medical School, Mater Dei Hospital, Tal-Qroqq, Malta.
- Unit of Molecular Medicine and Neuromuscular Disorders, Bambino Gesù Children's Hospital, Rome, Italy.
- Department of Dermatology, Université Paris V René Desartes, Paris, France.
- Pediatrics and Pediatric Neurology, Georg August University, Goettingen, Germany.
- Clinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham, UK.
- Bradford Child Development Centre, St. Luke's Hospital, Little Horton Lane, Bradford, UK.
- APHP, Paediatric Neurology, Hôpital Necker, Paris, France.
- Department of Child Neurology and Psychiatry, IRCCS Institute of Neurology, "C. Mondino" Foundation, Pavia, Italy.
- Neurology Department, Hospital Sant Joan de Déu, Esplugues, Barcelona, Spain.
- Clinical Genetics Unit-Department of Paediatrics, Hospital de Cruces, Baracaldo, Vizcaya, Spain.
- Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
- Department of Medical Genetics, Rikshospitalet, Oslo, Norway.
- Genetic Health, Victorian Clinical Genetics Service, Royal Children's Hospital, Parkville, Victoria, Australia.
- Department of Pediatrics/Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
- Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
- Paediatric Neurology, University Hospitals of Gasthuisberg, Leuven, Belgium.
- Pediatric Neurology Department, CHU Paris Sud-Hôpital, Bicêtre, France.
- Neurogenetics Unit, Medical Genetics Service, Hospital das Clinicas de Ribeirao Preto, School of Medicine of Ribeirao Preto, University of Sao Paulo, Campus Universitario, Monte Alegre, Ribeirão Preto–SP, Brazil.
- The Raphael Recanati Genetic Institute, Rabin Medical Center, Petach-Tikva, Israel.
- Department of Paediatrics, Nobles Hospital, Strang, Braddan, Isle of Man, UK.
- British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
- Department of Paediatrics, Rikshospitalet University Hospital, Oslo, Norway.
- The Genetic Institute, Ha'Emek Medical Center, Afula and the Rappaport Faculty of Medicine, Technion, Haifa, Israel.
- Department of Molecular and Human Genetics-T619, Baylor College of Medicine, Houston, Texas, USA.
- Genetic Health Services Victoria, Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia.
- Department of Neurology, Children's National Medical Center, Washington, DC, USA.
- The Kennedy Galton Centre, North West London Hospitals NHS Trust, Harrow, UK.
- Neurology Department, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK.
- Department of Paediatrics, Imperial College London, London, UK.
- Université Paris Descartes, Hôpital Cochin-St. Vincent de Paul, Paris, France.
Correspondence to: Yanick J Crow1 e-mail: yanickcrow@mac.com
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