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

Yanick Crow; Yanick J. Crow; Bruce E. Hayward; Rekha Parmar; Peter Robins; Andrea Leitch; Manir Ali; Deborah N. Black; Hans Van Bokhoven; Han G. Brunner; Ben C. Hamel; Peter C. Corry; Frances M. Cowan; Suzanne G. Frints; Joerg Klepper; John H. Livingston; Sally Ann Lynch; Roger F. Massey; Jean François Meritet; Jacques L. Michaud; Gerard Ponsot; Thomas Voit; Pierre Lebon; David T. Bonthron; Andrew P. Jackson; Deborah E. Barnes; Tomas Lindahl

doi:10.1038/ng1845

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

Yanick Crow, Yanick J. Crow, Bruce E. Hayward, Rekha Parmar, Peter Robins, Andrea Leitch, Manir Ali, Deborah N. Black, Hans Van Bokhoven, Han G. Brunner, Ben C. Hamel, Peter C. Corry, Frances M. Cowan, Suzanne G. Frints, Joerg Klepper, John H. Livingston, Sally Ann Lynch, Roger F. Massey, Jean François Meritet, Jacques L. MichaudGerard Ponsot, Thomas Voit, Pierre Lebon, David T. Bonthron, Andrew P. Jackson, Deborah E. Barnes, Tomas Lindahl

Research output: Contribution to journal › Article › peer-review

Abstract

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 to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. © 2006 Nature Publishing Group.

Original language	English
Pages (from-to)	917-920
Number of pages	3
Journal	Nature Genetics
Volume	38
Issue number	8
DOIs	https://doi.org/10.1038/ng1845
Publication status	Published - Aug 2006

Keywords

Animals
Base Sequence
genetics: DNA
deficiency: Exodeoxyribonucleases
enzymology: Heredodegenerative Disorders, Nervous System
Humans
Immunity, Innate
Mice
Mice, Knockout
Molecular Sequence Data
Mutation
deficiency: Phosphoproteins
genetics: Proteins
Syndrome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Crow, Y., Crow, Y. J., Hayward, B. E., Parmar, R., Robins, P., Leitch, A., Ali, M., Black, D. N., Van Bokhoven, H., Brunner, H. G., Hamel, B. C., Corry, P. C., Cowan, F. M., Frints, S. G., Klepper, J., Livingston, J. H., Lynch, S. A., Massey, R. F., Meritet, J. F., ... Lindahl, T. (2006). Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nature Genetics, 38(8), 917-920. https://doi.org/10.1038/ng1845

@article{fc988e63eeb248fe875ff62b6af8d785,

title = "Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Gouti{\`e}res syndrome at the AGS1 locus",

abstract = "Aicardi-Gouti{\`e}res 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 to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. {\textcopyright} 2006 Nature Publishing Group.",

keywords = "Animals, Base Sequence, genetics: DNA, deficiency: Exodeoxyribonucleases, enzymology: Heredodegenerative Disorders, Nervous System, Humans, Immunity, Innate, Mice, Mice, Knockout, Molecular Sequence Data, Mutation, deficiency: Phosphoproteins, genetics: Proteins, Syndrome",

author = "Yanick Crow and Crow, {Yanick J.} and Hayward, {Bruce E.} and Rekha Parmar and Peter Robins and Andrea Leitch and Manir Ali and Black, {Deborah N.} and {Van Bokhoven}, Hans and Brunner, {Han G.} and Hamel, {Ben C.} and Corry, {Peter C.} and Cowan, {Frances M.} and Frints, {Suzanne G.} and Joerg Klepper and Livingston, {John H.} and Lynch, {Sally Ann} and Massey, {Roger F.} and Meritet, {Jean Fran{\c c}ois} and Michaud, {Jacques L.} and Gerard Ponsot and Thomas Voit and Pierre Lebon and Bonthron, {David T.} and Jackson, {Andrew P.} and Barnes, {Deborah E.} and Tomas Lindahl",

year = "2006",

month = aug,

doi = "10.1038/ng1845",

language = "English",

volume = "38",

pages = "917--920",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

Crow, Y, Crow, YJ, Hayward, BE, Parmar, R, Robins, P, Leitch, A, Ali, M, Black, DN, Van Bokhoven, H, Brunner, HG, Hamel, BC, Corry, PC, Cowan, FM, Frints, SG, Klepper, J, Livingston, JH, Lynch, SA, Massey, RF, Meritet, JF, Michaud, JL, Ponsot, G, Voit, T, Lebon, P, Bonthron, DT, Jackson, AP, Barnes, DE & Lindahl, T 2006, 'Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus', Nature Genetics, vol. 38, no. 8, pp. 917-920. https://doi.org/10.1038/ng1845

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T1 - Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus

AU - Crow, Yanick

AU - Crow, Yanick J.

AU - Hayward, Bruce E.

AU - Parmar, Rekha

AU - Robins, Peter

AU - Leitch, Andrea

AU - Ali, Manir

AU - Black, Deborah N.

AU - Van Bokhoven, Hans

AU - Brunner, Han G.

AU - Hamel, Ben C.

AU - Corry, Peter C.

AU - Cowan, Frances M.

AU - Frints, Suzanne G.

AU - Klepper, Joerg

AU - Livingston, John H.

AU - Lynch, Sally Ann

AU - Massey, Roger F.

AU - Meritet, Jean François

AU - Michaud, Jacques L.

AU - Ponsot, Gerard

AU - Voit, Thomas

AU - Lebon, Pierre

AU - Bonthron, David T.

AU - Jackson, Andrew P.

AU - Barnes, Deborah E.

AU - Lindahl, Tomas

PY - 2006/8

Y1 - 2006/8

N2 - 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 to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. © 2006 Nature Publishing Group.

AB - 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 to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. © 2006 Nature Publishing Group.

KW - Animals

KW - Base Sequence

KW - genetics: DNA

KW - deficiency: Exodeoxyribonucleases

KW - enzymology: Heredodegenerative Disorders, Nervous System

KW - Humans

KW - Immunity, Innate

KW - Mice

KW - Mice, Knockout

KW - Molecular Sequence Data

KW - Mutation

KW - deficiency: Phosphoproteins

KW - genetics: Proteins

KW - Syndrome

U2 - 10.1038/ng1845

DO - 10.1038/ng1845

M3 - Article

SN - 1061-4036

VL - 38

SP - 917

EP - 920

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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