Journal article
Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response
GI Rice, J Bond, A Asipu, RL Brunette, IW Manfield, IM Carr, JC Fuller, RM Jackson, T Lamb, TA Briggs, M Ali, H Gornall, LR Couthard, A Aeby, SP Attard-Montalto, E Bertini, C Bodemer, K Brockmann, LA Brueton, PC Corry Show all
Nature Genetics | NATURE PUBLISHING GROUP | Published : 2009
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. © 2009 Nature America, Inc. All rights reserved.
Grants
Awarded by National Institute of Neurological Disorders and Stroke
Funding Acknowledgements
We thank the participating families with Aicardi-Goutieres syndrome for the use of genetic samples and clinical information. We thank all clinicians for contributing samples not included in the current manuscript. We thank C. Ponting and E. Morrison for helpful discussions and R. Smith for technical support in preparing images. This work was supported by BDF Newlife, the Royal Society, a Wellcome Trust VIP award to G. I. R., the National Institutes for Health Research Manchester Biomedical Research Centre, and the International AicardiGoutie` res syndrome Association (IAGSA).