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: Alberto Izzotti, Mariagrazia Longobardi, Cristina Cartiglia, Francesco Anzuini, Patrizio Arrigo, Elisa Fazzi, Simona Orcesi, Roberta La Piana, Alessandra Pulliero
• Journal: Journal of child neurology (J Child Neurol) Vol. 27 Issue 1 Pg. 51-60 (Jan 2012) ISSN: 1708-8283 [Electronic] United States
• PMID: 21862834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-alpha
• Toll-Like Receptors
• EXO1 protein, human
• Exodeoxyribonucleases
• ribonuclease HII
• Ribonuclease H
• DNA Repair Enzymes

Topics

• Analysis of Variance
• Autoimmune Diseases of the Nervous System (cerebrospinal fluid, genetics, pathology)
• Child
• Child, Preschool
• DNA Repair Enzymes (genetics)
• Exodeoxyribonucleases (genetics)
• Female
• Gene Expression
• Genotype
• Humans
• Interferon-alpha (cerebrospinal fluid)
• Lymphocytosis (cerebrospinal fluid)
• Male
• Microarray Analysis (methods)
• Mutation (genetics)
• Nervous System Malformations (cerebrospinal fluid, genetics, pathology)
• Ribonuclease H (genetics)
• Toll-Like Receptors (metabolism)