Clinical and molecular phenotype of Aicardi-Goutieres syndrome

Rice, Gillian, Patrick, Teresa, Parmar, Rekha, Taylor, Claire F., Aeby, Alec, Aicardi, Jean, Artuch, Rafael, Montalto, Simon Attard, Bacino, Carlos A., Barroso, Bruno, Baxter, Peter, Benko, William S., Bergmann, Carsten, Bertini, Enrico, Biancheri, Roberta, Blair, Edward M., Blau, Nenad, Bonthron, David T., Briggs, Tracy, Brueton, Louise A., Brunner, Han G., Burke, Christopher J., Carr, Ian M., Carvalho, Daniel R., Chandler, Kate E., Christen, Hans-Jurgen, Corry, Peter C., Cowan, Frances M., Cox, Helen, D'Arrigo, Stefano, Dean, John, De Laet, Corinne, De Praeter, Claudine, Dery, Catherine, Ferrie, Colin D., Flintoff, Kim, Frints, Suzanna G. M., Garcia-Cazorla, Angels, Gener, Blanca, Goizet, Cyril, Goutieres, Francoise, Green, Andrew J., Guet, Agnes, Hamel, Ben C. J., Hayward, Bruce E., Heiberg, Arvid, Hennekam, Raoul C., Husson, Marie, Jackson, Andrew P., Jayatunga, Rasieka, Jiang, Yong-Hui, Kant, Sarina G., Kao, Amy, King, Mary D., Kingston, Helen M., Klepper, Joerg, van der Knaap, Mario S., Kornberg, Andrew J., Kotzot, Dieter, Kratzer, Wilfried, Lacombe, Didier, Lagae, Lieven, Landrieu, Pierre Georges, Lanzi, Giovanni, Leitch, Andrea, Lim, Ming J., Livingston, John H., Lourenco, Charles M., Lyall, E. G. Hermione, Lynch, Sally A., Lyons, Michael J., Marom, Daphna, McClure, John P., McWilliam, Robert, Melancon, Serge B., Mewasingh, Leena D., Moutard, Marie-Laure, Nischal, Ken K., Ostergaard, John R., Prendiville, Julie, Rasmussen, Magnhild, Rogers, R. Curtis, Roland, Dominique, Rosser, Elisabeth M., Rostasy, Kevin, Roubertie, Agathe, Sanchis, Amparo, Schiffmann, Rafael, Scholl-Burgi, Sabine, Seal, Sunita, Shalev, Stavit A., Corcoles, C. Sierra, Sinha, Gyan P., Soler, Doriette, Spiegel, Ronen, Stephenson, John B. P., Tacke, Uta, Tan, Tiong Yang, Till, Marianne, Tolmie, John L., Tomlin, Pam, Vagnarelli, Federica, Valente, Enza Maria, Van Coster, Rudy N. A., Van der Aa, Nathalie, Vanderver, Adeline, Vles, Johannes S. H., Voit, Thomas, Wassmer, Evangeline, Weschke, Bernhard, Whiteford, Margo L., Willemsen, Michael A. A., Zankl, Andreas, Zuberi, Sameer M., Orcesi, Simona, Fazzi, Elisa, Lebon, Pierre and Crow, Yanick J. (2007) Clinical and molecular phenotype of Aicardi-Goutieres syndrome. American Journal of Human Genetics, 81 4: 713-725. doi:10.1086/521373

Author Rice, Gillian
Patrick, Teresa
Parmar, Rekha
Taylor, Claire F.
Aeby, Alec
Aicardi, Jean
Artuch, Rafael
Montalto, Simon Attard
Bacino, Carlos A.
Barroso, Bruno
Baxter, Peter
Benko, William S.
Bergmann, Carsten
Bertini, Enrico
Biancheri, Roberta
Blair, Edward M.
Blau, Nenad
Bonthron, David T.
Briggs, Tracy
Brueton, Louise A.
Brunner, Han G.
Burke, Christopher J.
Carr, Ian M.
Carvalho, Daniel R.
Chandler, Kate E.
Christen, Hans-Jurgen
Corry, Peter C.
Cowan, Frances M.
Cox, Helen
D'Arrigo, Stefano
Dean, John
De Laet, Corinne
De Praeter, Claudine
Dery, Catherine
Ferrie, Colin D.
Flintoff, Kim
Frints, Suzanna G. M.
Garcia-Cazorla, Angels
Gener, Blanca
Goizet, Cyril
Goutieres, Francoise
Green, Andrew J.
Guet, Agnes
Hamel, Ben C. J.
Hayward, Bruce E.
Heiberg, Arvid
Hennekam, Raoul C.
Husson, Marie
Jackson, Andrew P.
Jayatunga, Rasieka
Jiang, Yong-Hui
Kant, Sarina G.
Kao, Amy
King, Mary D.
Kingston, Helen M.
Klepper, Joerg
van der Knaap, Mario S.
Kornberg, Andrew J.
Kotzot, Dieter
Kratzer, Wilfried
Lacombe, Didier
Lagae, Lieven
Landrieu, Pierre Georges
Lanzi, Giovanni
Leitch, Andrea
Lim, Ming J.
Livingston, John H.
Lourenco, Charles M.
Lyall, E. G. Hermione
Lynch, Sally A.
Lyons, Michael J.
Marom, Daphna
McClure, John P.
McWilliam, Robert
Melancon, Serge B.
Mewasingh, Leena D.
Moutard, Marie-Laure
Nischal, Ken K.
Ostergaard, John R.
Prendiville, Julie
Rasmussen, Magnhild
Rogers, R. Curtis
Roland, Dominique
Rosser, Elisabeth M.
Rostasy, Kevin
Roubertie, Agathe
Sanchis, Amparo
Schiffmann, Rafael
Scholl-Burgi, Sabine
Seal, Sunita
Shalev, Stavit A.
Corcoles, C. Sierra
Sinha, Gyan P.
Soler, Doriette
Spiegel, Ronen
Stephenson, John B. P.
Tacke, Uta
Tan, Tiong Yang
Till, Marianne
Tolmie, John L.
Tomlin, Pam
Vagnarelli, Federica
Valente, Enza Maria
Van Coster, Rudy N. A.
Van der Aa, Nathalie
Vanderver, Adeline
Vles, Johannes S. H.
Voit, Thomas
Wassmer, Evangeline
Weschke, Bernhard
Whiteford, Margo L.
Willemsen, Michael A. A.
Zankl, Andreas
Zuberi, Sameer M.
Orcesi, Simona
Fazzi, Elisa
Lebon, Pierre
Crow, Yanick J.
Title Clinical and molecular phenotype of Aicardi-Goutieres syndrome
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2007-10
Sub-type Article (original research)
DOI 10.1086/521373
Volume 81
Issue 4
Start page 713
End page 725
Total pages 13
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.
Keyword Systemic-lupus-erythematosus
Infection-like syndrome
Progressive familial encephalopathy
Cerebrospinal-fluid lymphocytosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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