Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection

• Published in: Nature genetics Vol. 38; no. 8; pp. 910 - 916
• Main Authors: Bonthron, David T, Goizet, Cyril, Déry, Catherine, Woods, C Geoffrey, Ali, Manir, Weschke, Bernhard, Jackson, Andrew P, Voit, Thomas, King, Mary D, Baumann, Clarisse, Till, Marianne, Quarrell, Oliver W, Crow, Yanick J, Cau, Daniel, Lacombe, Didier, Lyall, Hermione, Lanzi, Giovanni, Stephenson, John B P, Griffith, Elen, Garner, Anna, Parmar, Rekha, Lebon, Pierre, McKeown, Carole, Rogers, R Curtis, Hayward, Bruce E, Babul-Hirji, Riyana, Bertini, Enrico, Martínez-Frías, María Luisa, Monier, Anne, Leitch, Andrea, Rittey, Christopher D, Semple, Colin, Aicardi, Jean, Chitayat, David, Tolmie, John L, Ponting, Chris P, Baxter, Peter, Tacke, Uta, Mathieu, Michèle, Sanchis, Amparo, Tomlin, Pam, Oade, Yvette, Klepper, Joerg, Fazzi, Elisa, Chandler, Kate E
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2006; Nature Publishing Group
• Subjects: Agriculture; Aicardi syndrome; Amino Acid Sequence; Animal Genetics and Genomics; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Complications and side effects; Diagnosis; DNA - genetics; Encephalitis, Viral - congenital; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene mutations; Genetic aspects; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Heredodegenerative Disorders, Nervous System - enzymology; Heredodegenerative Disorders, Nervous System - genetics; Human Genetics; Humans; Immune response; Immunology; Male; Malformations of the nervous system; Medical sciences; Models, Molecular; Molecular Sequence Data; Mutation; Neurological disorders; Neurology; Physiological aspects; Protein Structure, Quaternary; Protein Subunits; Ribonuclease; Ribonuclease H - chemistry; Ribonuclease H - genetics; Ribonuclease H - metabolism; Risk factors; Syndrome; United Kingdom; Nervous system diseases; Congenital; Enzyme; Esterases; Ribonuclease; Subunit; Congenital disease; Cerebral disorder; Infection; Eye disease; Gene; Malformation; Aicardi syndrome; Viral disease; Central nervous system disease; Hydrolases; Mutation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1842

Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.