Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus

@article{Crow2006MutationsIT,
  title={Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Gouti{\`e}res syndrome at the AGS1 locus},
  author={Yanick J. Crow and Bruce E. Hayward and Rekha Parmar and Peter Robins and Andrea Leitch and Manir Ali and Deborah N. Black and Hans van Bokhoven and Han G. Brunner and Ben C J Hamel and Peter C Corry and Frances M. Cowan and Suzanne G M Frints and Joerg Klepper and John H. Livingston and Sally Ann Lynch and Roger F Massey and Jean François Meritet and Jacques L. Michaud and G{\'e}rard Ponsot and Thomas Voit and Pierre Lebon and David T. Bonthron and Andrew P. Jackson and Deborah E. Barnes and Tomas Lindahl},
  journal={Nature Genetics},
  year={2006},
  volume={38},
  pages={917-920}
}
Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3′ → 5′ DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1−/− mouse leads… Expand
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TLDR
The generation of gene-targeted Trex1−/− mice exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure. Expand
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It is shown that AGS can result from mutations in the genes encoding any one of its three subunits, demonstrating a role for ribonuclease H in human neurological disease and suggesting an unanticipated relationship between ribonUClease H2 and the antiviral immune response that warrants further investigation. Expand
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TLDR
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