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

By G. Rice, J. Bond, A. Asipu, Rebecca L. Brunette, I. Manfield, I. Carr, Jonathan C. Fuller, R. Jackson, Teresa Lamb, T. Briggs and 41 more. Nature Genetics, 2009

711 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/595db5a7b6dd95b64e0c6251275c58192fa8a22e

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In Molecular Biology

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Citations in the corpus

• The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer (2018, background): “Mutations involved in Aicardi-Goutières syndrome implicate SAM HD1 as regulator of the innate immune response.”
• HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (2011, background): “SAMHD1 is also associated with Aicardi–Goutieres syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-&agr”
• Evolution and impact of subclonal mutations in chronic lymphocytic leukemia (2013, positive): “Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes.”
• Pattern recognition receptors and inflammation. (2010, background): “In addition, mutations in components of RNase H2 are also involved in AGS (Rice et al., 2009).”
• A census of human RNA-binding proteins (2014, background): “SAMHD1 Aicardi-Goutieres syndrome (AGS), Chilbain lupus 2 missense mutation (Ravenscroft et al., 2011; Rice et al., 2009)”