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 |