Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

  • Nat Genet. 2009 Jul;41(7):829-32. doi: 10.1038/ng.373.
Gillian I Rice  1 ,  Jacquelyn Bond ,  Aruna Asipu ,  Rebecca L Brunette ,  Iain W Manfield ,  Ian M Carr ,  Jonathan C Fuller ,  Richard M Jackson ,  Teresa Lamb ,  Tracy A Briggs ,  Manir Ali ,  Hannah Gornall ,  Lydia R Couthard ,  Alec Aeby ,  Simon P Attard-Montalto ,  Enrico Bertini ,  Christine Bodemer ,  Knut Brockmann ,  Louise A Brueton ,  Peter C Corry ,  Isabelle Desguerre ,  Elisa Fazzi ,  Angels Garcia Cazorla ,  Blanca Gener ,  Ben C J Hamel ,  Arvid Heiberg ,  Matthew Hunter ,  Marjo S van der Knaap ,  Ram Kumar ,  Lieven Lagae ,  Pierre G Landrieu ,  Charles M Lourenco ,  Daphna Marom ,  Michael F McDermott ,  William van der Merwe ,  Simona Orcesi ,  Julie S Prendiville ,  Magnhild Rasmussen ,  Stavit A Shalev ,  Doriette M Soler ,  Marwan Shinawi ,  Ronen Spiegel ,  Tiong Y Tan ,  Adeline Vanderver ,  Emma L Wakeling ,  Evangeline Wassmer ,  Elizabeth Whittaker ,  Pierre Lebon ,  Daniel B Stetson ,  David T Bonthron ,  Yanick J Crow
Affiliations
  • 1. Academic Unit of Medical Genetics, University of Manchester, Manchester, UK.
PMID: 19525956 DOI: 10.1038/ng.373
Abstract

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.