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

Gillian I. Rice; Jacquelyn Bond; Aruna Asipu; Rebecca L. Brunette; Iain W. Manfield; Ian M. Carr; Jonathan C. Fuller; Richard M. Jackson; Teresa Lamb; Tracy A. Briggs; Manir Ali; Hannah Gornall; Lydia R. Couthard; Alec Aeby; Simon P. Attard-Montalto; Enrico Bertini; Christine Bodemer; Knut Brockmann; Louise A. Brueton; Peter C. Corry; Isabelle Desguerre; Elisa Fazzi; Angels Garcia Cazorla; Blanca Gener; Ben C.J. Hamel; Arvid Heiberg; Matthew Hunter; Marjo S. Van Der Knaap; Ram Kumar; Lieven Lagae; Pierre G. Landrieu; Charles M. Lourenco; Daphna Marom; Michael F. McDermott; William Van Der Merwe; Simona Orcesi; Julie S. Prendiville; Magnhild Rasmussen; Stavit A. Shalev; Doriette M. Soler; Marwan Shinawi; Ronen Spiegel; Tiong Y. Tan; Adeline Vanderver; Emma L. Wakeling; Evangeline Wassmer; Elizabeth Whittaker; Pierre Lebon; Daniel B. Stetson; David T. Bonthron; Yanick J. Crow

doi:10.1038/ng.373

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

Gillian I. Rice, Jacquelyn Bond, Aruna Asipu, Rebecca L. Brunette, Iain W. Manfield, Ian M. Carr, Jonathan C. Fuller, Richard M. Jackson, Teresa Lamb, Tracy A. Briggs, Manir Ali, Hannah Gornall, Lydia R. Couthard, Alec Aeby, Simon P. Attard-Montalto, Enrico Bertini, Christine Bodemer, Knut Brockmann, Louise A. Brueton, Peter C. CorryIsabelle Desguerre, Elisa Fazzi, Angels Garcia Cazorla, Blanca Gener, Ben C.J. Hamel, Arvid Heiberg, Matthew Hunter, Marjo S. Van Der Knaap, Ram Kumar, Lieven Lagae, Pierre G. Landrieu, Charles M. Lourenco, Daphna Marom, Michael F. McDermott, William Van Der Merwe, Simona Orcesi, Julie S. Prendiville, Magnhild Rasmussen, Stavit A. Shalev, Doriette M. Soler, Marwan Shinawi, Ronen Spiegel, Tiong Y. Tan, Adeline Vanderver, Emma L. Wakeling, Evangeline Wassmer, Elizabeth Whittaker, Pierre Lebon, Daniel B. Stetson, David T. Bonthron, Yanick J. Crow

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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.

Original language	English
Pages (from-to)	829-832
Number of pages	4
Journal	Nature Genetics
Volume	41
Issue number	7
DOIs	https://doi.org/10.1038/ng.373
State	Published - Jul 2009

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Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., Couthard, L. R., Aeby, A., Attard-Montalto, S. P., Bertini, E., Bodemer, C., Brockmann, K., Brueton, L. A., ... Crow, Y. J. (2009). Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response. Nature Genetics, 41(7), 829-832. https://doi.org/10.1038/ng.373

@article{94c1162e303d4562a2652da4c2263f73,

title = "Mutations involved in Aicardi-Gouti{\`e}res syndrome implicate SAMHD1 as regulator of the innate immune response",

abstract = "Aicardi-Gouti{\`e}res 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.",

author = "Rice, {Gillian I.} and Jacquelyn Bond and Aruna Asipu and Brunette, {Rebecca L.} and Manfield, {Iain W.} and Carr, {Ian M.} and Fuller, {Jonathan C.} and Jackson, {Richard M.} and Teresa Lamb and Briggs, {Tracy A.} and Manir Ali and Hannah Gornall and Couthard, {Lydia R.} and Alec Aeby and Attard-Montalto, {Simon P.} and Enrico Bertini and Christine Bodemer and Knut Brockmann and Brueton, {Louise A.} and Corry, {Peter C.} and Isabelle Desguerre and Elisa Fazzi and Cazorla, {Angels Garcia} and Blanca Gener and Hamel, {Ben C.J.} and Arvid Heiberg and Matthew Hunter and {Van Der Knaap}, {Marjo S.} and Ram Kumar and Lieven Lagae and Landrieu, {Pierre G.} and Lourenco, {Charles M.} and Daphna Marom and McDermott, {Michael F.} and {Van Der Merwe}, William and Simona Orcesi and Prendiville, {Julie S.} and Magnhild Rasmussen and Shalev, {Stavit A.} and Soler, {Doriette M.} and Marwan Shinawi and Ronen Spiegel and Tan, {Tiong Y.} and Adeline Vanderver and Wakeling, {Emma L.} and Evangeline Wassmer and Elizabeth Whittaker and Pierre Lebon and Stetson, {Daniel B.} and Bonthron, {David T.} and Crow, {Yanick J.}",

note = "Funding Information: We thank the participating families with Aicardi-Gouti{\`e}res 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 Aicardi-Gouti{\`e}res syndrome Association (IAGSA).",

year = "2009",

month = jul,

doi = "10.1038/ng.373",

language = "English",

volume = "41",

pages = "829--832",

journal = "Nature Genetics",

issn = "1061-4036",

number = "7",

}

Rice, GI, Bond, J, Asipu, A, Brunette, RL, Manfield, IW, Carr, IM, Fuller, JC, Jackson, RM, Lamb, T, Briggs, TA, Ali, M, Gornall, H, Couthard, LR, Aeby, A, Attard-Montalto, SP, Bertini, E, Bodemer, C, Brockmann, K, Brueton, LA, Corry, PC, Desguerre, I, Fazzi, E, Cazorla, AG, Gener, B, Hamel, BCJ, Heiberg, A, Hunter, M, Van Der Knaap, MS, Kumar, R, Lagae, L, Landrieu, PG, Lourenco, CM, Marom, D, McDermott, MF, Van Der Merwe, W, Orcesi, S, Prendiville, JS, Rasmussen, M, Shalev, SA, Soler, DM, Shinawi, M, Spiegel, R, Tan, TY, Vanderver, A, Wakeling, EL, Wassmer, E, Whittaker, E, Lebon, P, Stetson, DB, Bonthron, DT & Crow, YJ 2009, 'Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response', Nature Genetics, vol. 41, no. 7, pp. 829-832. https://doi.org/10.1038/ng.373

TY - JOUR

T1 - Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

AU - Rice, Gillian I.

AU - Bond, Jacquelyn

AU - Asipu, Aruna

AU - Brunette, Rebecca L.

AU - Manfield, Iain W.

AU - Carr, Ian M.

AU - Fuller, Jonathan C.

AU - Jackson, Richard M.

AU - Lamb, Teresa

AU - Briggs, Tracy A.

AU - Ali, Manir

AU - Gornall, Hannah

AU - Couthard, Lydia R.

AU - Aeby, Alec

AU - Attard-Montalto, Simon P.

AU - Bertini, Enrico

AU - Bodemer, Christine

AU - Brockmann, Knut

AU - Brueton, Louise A.

AU - Corry, Peter C.

AU - Desguerre, Isabelle

AU - Fazzi, Elisa

AU - Cazorla, Angels Garcia

AU - Gener, Blanca

AU - Hamel, Ben C.J.

AU - Heiberg, Arvid

AU - Hunter, Matthew

AU - Van Der Knaap, Marjo S.

AU - Kumar, Ram

AU - Lagae, Lieven

AU - Landrieu, Pierre G.

AU - Lourenco, Charles M.

AU - Marom, Daphna

AU - McDermott, Michael F.

AU - Van Der Merwe, William

AU - Orcesi, Simona

AU - Prendiville, Julie S.

AU - Rasmussen, Magnhild

AU - Shalev, Stavit A.

AU - Soler, Doriette M.

AU - Shinawi, Marwan

AU - Spiegel, Ronen

AU - Tan, Tiong Y.

AU - Vanderver, Adeline

AU - Wakeling, Emma L.

AU - Wassmer, Evangeline

AU - Whittaker, Elizabeth

AU - Lebon, Pierre

AU - Stetson, Daniel B.

AU - Bonthron, David T.

AU - Crow, Yanick J.

N1 - Funding Information: We thank the participating families with Aicardi-Goutières 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 Aicardi-Goutières syndrome Association (IAGSA).

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67649861901&partnerID=8YFLogxK

U2 - 10.1038/ng.373

DO - 10.1038/ng.373

M3 - Article

C2 - 19525956

AN - SCOPUS:67649861901

SN - 1061-4036

VL - 41

SP - 829

EP - 832

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

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

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