title: Novel interferonopathies associated with mutations in RIG-I like receptors.
abstract: Type I interferonopathies are a relatively new class of inherited autoimmune disorders associated with an inborn elevated interferon response. Activation of cytosolic receptors which recognize viral double stranded RNA including the RIG-I (retinoic acid-inducible gene I) like receptors RIG-I and MDA5 (melanoma differentiation-associated gene 5) has been shown to induce the transcription of type I interferon genes. Within recent years, with the help of next generation sequencing techniques in syndromic families, mutations in the genes encoding for RIG-I and MDA5 have been identified to cause rare diseases including Aicardi-Goutières syndrome, Systemic Lupus Erythematosus in certain individuals as well as classic and atypical Singleton-Merten syndrome. Patients carrying mono-allelic mutations in MDA5 and RIG-I show constitutive activation of the RIG-I receptors and downstream signalling associated with increased type I interferon production. Although differing in the degree of phenotypic expression and severity, the phenotype of these "novel" diseases shows a considerable overlap reflecting their common pathogenetic pathway.
authors.affiliation: Department of General Pediatrics, Muenster University Children's Hospital, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany. Electronic address: Insa.Buers@ukmuenster.de.
authors.forename: Insa
authors.initials: I
authors.lastname: Buers
authors.affiliation: Department of General Pediatrics, Muenster University Children's Hospital, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany. Electronic address: Yvonne.Nitschke@ukmuenster.de.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Nitschke
authors.affiliation: Department of General Pediatrics, Muenster University Children's Hospital, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany. Electronic address: frank.rutsch@ukmuenster.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000071457:DEAD Box Protein 58 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics / Q000276:immunology; D009154:Mutation; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology
chemical_list: D007370:Interferon Type I; D011971:Receptors, Immunologic; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Aicardi-Goutières; SLE; Singleton-Merten