Table 4 Type I inferferonopathies
From: Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity
Disease | Gene | Protein function | Inheritance | Main clinical findings | Reference |
|---|---|---|---|---|---|
Aicardi-Goutières syndrome (AGS) | TREX1 | 3′ repair exonuclease (cytosolic DNase) | AR, de novo dominant | Leukoencephalopathy, microcephaly, calcification of basal ganglia, seizures, fever, severe developmental delay, chilblain lesions | |
RNASEH2A | Ribonuclease H2, subunit A | AR | |||
RNASEH2B | Ribonuclease H2, subunit B | AR | |||
RNASEH2C | Ribonuclease H2, subunit C | AR | |||
ADAR1 | adenosine deaminase, RNA-specific | AR, de novo dominant | |||
IFIH1 | IFN-induced helicase C domain-containing protein 1 (PRR for dsRNA) | AD, de novo dominant | |||
SAMHD1 | SAM domain and HD domain-containing protein 1 (RNase) | AR | |||
STING-associated vasculopathy, infantile-onset (SAVI) | STING | Stimulator of interferon genes (induction of type I interferons in response to infection with intracellular pathogens) | AD, de novo dominant | Vasculitis characterized by ulcerating acral lesions, ILD, chilblain lesions, malar rash, arthralgia | |
Familial chilblain lupus (CHBL) | TREX1 | 3′ repair exonuclease (cytosolic DNase) | AD | Cutaneous lupus erythematosus with chilblain lesions, arthralgia | |
STING | Stimulator of interferon genes (induction of type I interferons in response to infection with intracellular pathogens) | AD | |||
SAMHD1 | SAM domain and HD domain-containing protein 1 (RNase) | AD | |||
Spondyloenchondrodysplasia (SPENCD) | ACP5 | Tartrate-resistant acid phosphatase, type 5 (dephosphorylation of osteopontin) | AR | Spondylometaphyseal dysplasia, basal ganglia calcification, variable neurological impairment, arthritis, thrombocytopenia, variable immunodeficiency resulting in recurrent pneumonias, severe VZV infection/reactivation, mucocutaneous abscesses (in a minority of patients) | |
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) | PSMA3 | Proteasome subunit α7 (immunoproteasome subunit) | AR | Eczema, panniculitis, lipodystrophy, fever, calcification of basal ganglia | |
PSMB4 | Proteasome subunit β7 (immunoproteasome subunit) | AR | |||
PSMB8 | Proteasome subunit β5i (immunoproteasome subunit) | AR | |||
PSMB9 | Proteasome subunit β1i (immunoproteasome subunit) | AR | |||
POMP | Proteasome maturation protein (immunoproteasome formation) | AR | |||
Renal vasculopathy with cerebral leukodystrophy (RVCL) | TREX1 | 3’ repair exonuclease (cytosolic DNase) | AD | Retinopathy, leukodystrophy, cerebrovascular disease, glomerulopathy | |
Singleton-Merten syndrome (SGMRT) | IFIH1 | IFN-induced helicase C domain-containing protein 1 (PRR for dsRNA) | AD | Progressive vasculopathy with the calcification of large vessels, dental and skeletal abnormalities, osteoporosis, photosensitivity, psoriasis | |
RIG1 | Retinoic acid-inducible gene 1 (PRR for dsRNA) | AD | |||
ISG15 deficiency | ISG15 | Interferon-stimulated gene 15 (protein ISGylation, IFNÎł induction) | AR | Calcification of basal ganglia, necrotizing skin lesions, MSMD | |
USP18 deficiency | USP18 | Ubiquitin-specific protease 18 (de- ISGylation) | AR | Microcephaly, cerebral calcification, thrombocytopenia | |
X-linked reticulate pigmentary disorder (XLPDR) | POLA1 | DNA polymerase α (DNA replication) | XR | Hyperpigmented skin lesions, enteropathy, hypogammaglobulinemia-associated respiratory tract infections and invasive fungal infections (in a minority of patients) | 270 Formularbeginn Formularende |
DNase II deficiency | DNASE2 | Deoxyribonuclease II (lysosomal endonuclease) | AR | Hepatosplenomegaly, cutaneous vasculitis lesions, recurrent fever, endocrinopathy, anemia, thrombocytopenia, glomerulonephritis, hypogammaglobulinemia necessitating immunoglobulin replacement (in a minority of patients) |
