Abstract
Aicardi-Goutières syndrome is a rare encephalopathy of mutational origin characterized by increased levels of interferon alpha in cerebrospinal fluid. The aim of this study was to explore the influence of different Aicardi-Goutières syndrome genotypes on the clinical course of patients, seeking to identify specific gene expression profiles able to explain Aicardi-Goutières syndrome phenotype differences. We detected the occurrence of Aicardi-Goutières syndrome mutations in 21 patients and compared microarray gene-expression data of cerebrospinal fluid lymphocytes with clinical variables. The levels of interferon alpha in cerebrospinal fluid were high in all patients; we found differences in the expression of genes encoding for Toll-like receptor, endogenous RNases, T lymphocyte activation, angiogenesis inhibition, and peripheral interferon alpha production. These results indicate that further to interferon alpha production in the central nervous system, a variety of other pathogenic mechanisms is activated in Aicardi-Goutières syndrome to various degrees in different patients, thus explaining the interindividual difference in Aicardi-Goutières syndrome course.
| Original language | English |
|---|---|
| Pages (from-to) | 51-60 |
| Number of pages | 10 |
| Journal | Journal of Child Neurology |
| Volume | 27 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2012 |
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Keywords
- Aicardi-Goutières syndrome mutations
- Brain damage
- Interferon alpha
ASJC Scopus subject areas
- Clinical Neurology
- Pediatrics, Perinatology, and Child Health
Cite this
Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in aicardi-goutières syndrome. / Izzotti, Alberto; Longobardi, Mariagrazia; Cartiglia, Cristina; Anzuini, Francesco; Arrigo, Patrizio; Fazzi, Elisa; Orcesi, Simona; Piana, Roberta La; Pulliero, Alessandra.
In: Journal of Child Neurology, Vol. 27, No. 1, 01.2012, p. 51-60.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in aicardi-goutières syndrome
AU - Izzotti, Alberto
AU - Longobardi, Mariagrazia
AU - Cartiglia, Cristina
AU - Anzuini, Francesco
AU - Arrigo, Patrizio
AU - Fazzi, Elisa
AU - Orcesi, Simona
AU - Piana, Roberta La
AU - Pulliero, Alessandra
PY - 2012/1
Y1 - 2012/1
N2 - Aicardi-Goutières syndrome is a rare encephalopathy of mutational origin characterized by increased levels of interferon alpha in cerebrospinal fluid. The aim of this study was to explore the influence of different Aicardi-Goutières syndrome genotypes on the clinical course of patients, seeking to identify specific gene expression profiles able to explain Aicardi-Goutières syndrome phenotype differences. We detected the occurrence of Aicardi-Goutières syndrome mutations in 21 patients and compared microarray gene-expression data of cerebrospinal fluid lymphocytes with clinical variables. The levels of interferon alpha in cerebrospinal fluid were high in all patients; we found differences in the expression of genes encoding for Toll-like receptor, endogenous RNases, T lymphocyte activation, angiogenesis inhibition, and peripheral interferon alpha production. These results indicate that further to interferon alpha production in the central nervous system, a variety of other pathogenic mechanisms is activated in Aicardi-Goutières syndrome to various degrees in different patients, thus explaining the interindividual difference in Aicardi-Goutières syndrome course.
AB - Aicardi-Goutières syndrome is a rare encephalopathy of mutational origin characterized by increased levels of interferon alpha in cerebrospinal fluid. The aim of this study was to explore the influence of different Aicardi-Goutières syndrome genotypes on the clinical course of patients, seeking to identify specific gene expression profiles able to explain Aicardi-Goutières syndrome phenotype differences. We detected the occurrence of Aicardi-Goutières syndrome mutations in 21 patients and compared microarray gene-expression data of cerebrospinal fluid lymphocytes with clinical variables. The levels of interferon alpha in cerebrospinal fluid were high in all patients; we found differences in the expression of genes encoding for Toll-like receptor, endogenous RNases, T lymphocyte activation, angiogenesis inhibition, and peripheral interferon alpha production. These results indicate that further to interferon alpha production in the central nervous system, a variety of other pathogenic mechanisms is activated in Aicardi-Goutières syndrome to various degrees in different patients, thus explaining the interindividual difference in Aicardi-Goutières syndrome course.
KW - Aicardi-Goutières syndrome mutations
KW - Brain damage
KW - Interferon alpha
UR - http://www.scopus.com/inward/record.url?scp=84856893266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856893266&partnerID=8YFLogxK
U2 - 10.1177/0883073811413582
DO - 10.1177/0883073811413582
M3 - Article
C2 - 21862834
AN - SCOPUS:84856893266
VL - 27
SP - 51
EP - 60
JO - Journal of Child Neurology
JF - Journal of Child Neurology
SN - 0883-0738
IS - 1
ER -