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Table 1 Type I interferonopathies. Mutated gene, protein function, pattern of inheritance and main symptoms of know type I interferonopathies

From: Type I interferonopathies in pediatric rheumatology

Disease Gene Protein function Inheritance Symptoms
Aicardi-Goutières syndrome (AGS)1 TREX-1 3′-5′ DNA exonuclease AR and AD Classical AGS
AGS2 RNASEH2B Components of Rnase H2 complex. Removes ribonucleotides from RNA-DNA hybrids AR Classical AGS
AGS4 RNASEH2A Classical AGS with dysmorphic features
AGS5 SAMHD1 Restricts the availability of cytosolic deoxynucleotides AR Mild AGS, mouth ulcer, deforming arthropathy, cerebral vasculopathy with early onset stroke
AGS6 ADAR Deaminates adenosine to inosine in endogenous dsRNA preventing recognition by MDA5 receptor AR and AD Classical AGS, bilateral striatal necrosis
AGS7 IFIH1 Cytosolic receptor for dsRNA AD Classical or mild AGS, asymptomatic
Retinal vasculopathy with cerebral leukodystrophy (RVCL) TREX-1 3′-5′ DNA exonuclease AD Adult-onset loss of vision, stroke, motor impairment, cognitive decline, Raynaud and liver involvement
Spondyloenchondrodysplasia (SPENCD) ACP5 Lysosomal phosphatase activity AR Spondyloenchondrodysplasia, immune disregulation and in some cases combined immunodeficiency
STING associated vasculopathy with onset in infancy (SAVI) TMEM173 Transduction of cytoplasmic DNA-induced signal AD Systemic inflammation, cutanous vasculopathy, pulmonary inflammation
Proteasome Associated Autoinflammatory Syndromes (PRAAS) PSMB8 Part of the proteasome complex AR Autoinflammation, lipodistrophy, dermatosis, hyper-immunoglobulinemia, joint contractures (JMP), short stature
ISG15 deficieny ISG15 Stabilizes USP18, a negative regulator of type I interferon AR Brain calcifications, seizures, mycobacterial susceptibility
Singleton-Merten syndrome (SMS) IFIH1 Cytosolic receptor for dsRNA AD Dental dysplasia, aortic calcifications, skeletal abnormalities, glaucoma, psoriasis
Atypical SMS DDX58 Cytosolic receptor for dsRNA AD Aortic calcifications, skeletal abnormalities, glaucoma, psoriasis
Trichohepatoenteric syndrome (THES) SKIV2L RNA helicase AR Severe intractable diarrhea, hair abnormalities (trichorrhexis nodosa), facial dysmorphism, immunodeficiency in most cases
  1. ADAR1 adenosine deaminase acting on RNA 1, ACP5 Acid Phosphatase 5, Tartrate Resistant, AGS Aicardi-Goutières syndrome, DDX58 DEAD Box Protein 58, IFIH1 IFN-induced helicase C domain-containing protein 1 (also known as MDA5), ISG15 Interferon-stimulated gene 15, PSMB8 Proteasome subunit beta type-8, RNASEH2 Ribonuclease H2, RVCL Retinal vasculopathy with cerebral leukodystrophy, SAMHD1 deoxynucleoside triphosphate triphosphohydrolase SAM domain and HD domain 1, SPENCD spondyloenchondrodysplasia, SAVI STING associated vasculopathy with onset in infancy, PRAAS Proteasome Associated Autoinflammatory Syndromes, SMS Singleton-Merten syndrome, THES Trichohepatoenteric syndrome, TMEM173 transmembrane Protein 173, TREX1 DNA 3ʹ - repair exonuclease 1