Table 1.
Type I interferonopathies. Mutated gene, protein function, pattern of inheritance and main symptoms of know type I interferonopathies
| 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 |
| AGS3 | RNASEH2C | 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 |
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