1. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response
- Author
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Stavit A. Shalev, Iain W. Manfield, Tracy A Briggs, Manir Ali, Richard M. Jackson, Elisa Fazzi, Peter Corry, Adeline Vanderver, Simona Orcesi, Daphna Marom, Angels Garcia Cazorla, Simon Attard-Montalto, Marwan Shinawi, Louise Brueton, Isabelle Desguerre, Ian M. Carr, Lieven Lagae, Charles Marques Lourenço, Tiong Yang Tan, Lydia R Couthard, Pierre Landrieu, Jonathan C. Fuller, Ben C.J. Hamel, Evangeline Wassmer, Rebecca L. Brunette, Pierre Lebon, Jacquelyn Bond, William G. Van Der Merwe, Emma Wakeling, Elizabeth Whittaker, Matthew F. Hunter, Ronen Spiegel, Enrico Bertini, Daniel B. Stetson, Ram L. Kumar, Blanca Gener, Gillian I. Rice, Julie S. Prendiville, Christine Bodemer, Doriette Soler, Arvid Heiberg, Marjo S. van der Knaap, Teresa Lamb, Knut Brockmann, Hannah Gornall, Magnhild Rasmussen, David T. Bonthron, Alec Aeby, Michael F. McDermott, Aruna Asipu, Yanick J. Crow, Other departments, University of Groningen, Pediatric surgery, and NCA - Childhood White Matter Diseases
- Subjects
INTERFERON ,GENES ,AUTOIMMUNITY ,Ribonucleotide excision repair ,Regulator ,VIRUS-INFECTION ,Biology ,medicine.disease_cause ,Article ,Aicardi syndrome ,Autoimmunity ,SAM Domain and HD Domain-Containing Protein 1 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,DOMAIN ,GAMMA-INDUCED PROTEIN ,EXONUCLEASE TREX1 ,Genetics ,medicine ,Humans ,CONGENITAL INFECTION ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,Gene ,030304 developmental biology ,Monomeric GTP-Binding Proteins ,0303 health sciences ,Innate immune system ,Brain Diseases, Metabolic, Inborn ,medicine.disease ,Immunity, Innate ,3. Good health ,Amino Acid Substitution ,Immunology ,Aicardi–Goutières syndrome ,030217 neurology & neurosurgery - Abstract
Aicardi-Goutieres 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.
- Published
- 2009
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