Table 1.
Mutated gene and corresponding locus, protein function, pattern of inheritance, and common symptoms of main type I interferonopathies.
| Disease | Gene | Locus | Protein function | Inheritance | Phenotype |
|---|---|---|---|---|---|
| AGS 1 | TREX-1 | 3p21.31 | 3′-5′ DNA exonuclease | AR /AD | Basal ganglia calcifications, delayed psycho-motor development, epilepsy (classic AGS) |
| AGS2 | RNASEH2B | 13q14.3 | Components of Rnase H2 complex Removes ribonucleotides from RNA-DNA hybrids |
AR | Classic AGS |
| AGS3 | RNASEH2C | 11.q.13.1 | Classic ASG | ||
| AGS4 | RNASEH2A | 19p13.13 | ASG, dysmorfic features | ||
| AGS5 | SAMHD1 | 20q11.23 | Restricts the availability of cytosolic deoxynucleotides | AR | Severe neurological involvement with early stroke, arthropathy |
| AGS6 | ADAR | 1q21.3 | RNA-specific adenosine deaminase 1-dsRNA preventing recognition by MDA5 receptor | AR /AD | ASG, bilateral striatal necrosis |
| AGS7 | IFIH1 | 2q24.3 | Cytosolic receptor for dsRNA | AD | Mild AGS |
| SPENCD | ACP5 | 2q24.2 | Negative regulation of Osteopontine | AR | Spondyloenchondrodysplasia, autoimmunity |
| SAVI | TMEM173 or STING | 5q31.1 | Transduction of cytoplasmic DNA-induced signal | AD | Skin vasculopaty, bilateral interstitial lung disease |
| PRAAS |
PSMB8
PSMB9 PSMB7 PSMA3 POMP PSMG2 |
6p21.32 6p21.32 9q33.3 14q23.1 13q12.3 18p11.21 |
Proteasome complex subunit Proteosome chaperone |
AR | (CANDLE syndrome) Chronic Neutrophilic Dermatosis panniculitis with Lipodystrophy, Elevated Temperature and myalgia, hepatomegaly, splenomegaly, brain calcifications |
| ISG15 deficiency | ISG15 | 1p31.33 | Stabilizes USP18 | AR | Neurological involvement, mycobacterial susceptibility |
| USP18 deficiency | UDP18 | 2q37.1 | Negative regulator of IFNR signaling | AD | Neurological involvement (pseudo TORCH syndrome), hepatomegaly, thrombocytopenia |
| SMS | IFIH1 | 2q24.3 | Cytosolic receptor for dsRNA | AD | Dental and skeletal dysplasia, aortic calcification, glaucome and psoriasis |
| Atypical SMS | DDX58 | 9p21.1 | Cytosolic receptor for dsRNA | AD | SMS without dental dysplasia |
| THES | SKIV2L | 6p21.33 | RNA helicase | AR | Severe intractable diarrhea, trichorrehexis nodosa, facial dysmorfism, immunodeficit |
| DNAse II deficiency | DNAse II | 19p13.13 | Endonuclease | AR | Severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy |
| XLPDR | POLA1 | Xp22.11-p21.3 | DNA Polymerase Alpha 1 | X-linked | Generalized hyperpigmentation with small hypomelanotic macules during early childhood, dysmorphic feature, recurrent respiratory infections, and severe gastrointestinal disorders |
AD, autosomal dominant; AR, autosomal recessive; 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; ISG15, Interferon-stimulated gene 15; PSMB8, Proteasome subunit beta type-8; PSMB9, Proteasome subunit beta type-9; PSMB7, Proteasome subunit beta type-7; PSMA3, Proteasome 20S Subunit Alpha 3; POMP, Proteasome Maturation Protein; PSMG2, Proteasome Assembly Chaperone 2; RNASEH2, Ribonuclease H2; 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 3′-repair exonuclease 1; TRAP, Acid Phosphatase 5 Tartrate Resistant; IFIH1, IFN-induced helicase C domain-containing protein 1; MDA5, melanoma differentiation-associated protein 5; XLPDR, X-linked reticulate pigmentary disorder.