title: Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in Aicardi-Goutieres syndrome.
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.
authors.affiliation: Department of Health Sciences, University of Genoa, Genoa, 16132, Italy. izzotti@unige.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Longobardi
authors.forename: Cristina
authors.initials: C
authors.lastname: Cartiglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Anzuini
authors.forename: Patrizio
authors.initials: P
authors.lastname: Arrigo
authors.forename: Elisa
authors.initials: E
authors.lastname: Fazzi
authors.forename: Simona
authors.initials: S
authors.lastname: Orcesi
authors.forename: Roberta La
authors.initials: RL
authors.lastname: Piana
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pulliero
mesh_terms: D000704:Analysis of Variance; D020274:Autoimmune Diseases of the Nervous System / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D045643:DNA Repair Enzymes / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000134:cerebrospinal fluid; D008218:Lymphocytosis / Q000134:cerebrospinal fluid; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D016914:Ribonuclease H / Q000235:genetics*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D051193:Toll-Like Receptors; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C091139:ribonuclease HII; D016914:Ribonuclease H; D045643:DNA Repair Enzymes