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. Epub 2009 Jun 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Brain Diseases, Metabolic, Inborn / immunology
  • Humans
  • Immunity, Innate*
  • Monomeric GTP-Binding Proteins / genetics*
  • Monomeric GTP-Binding Proteins / immunology
  • SAM Domain and HD Domain-Containing Protein 1

Substances

  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins

Associated data

  • RefSeq/NM_015474
  • RefSeq/NP_056289