Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in aicardi-goutières syndrome

Alberto Izzotti, Mariagrazia Longobardi, Cristina Cartiglia, Francesco Anzuini, Patrizio Arrigo, Elisa Fazzi, Simona Orcesi, Roberta La Piana, Alessandra Pulliero

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)51-60
Number of pages10
JournalJournal of Child Neurology
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Aicardi-Goutières syndrome mutations
  • Brain damage
  • Interferon alpha

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

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