Trial reportThe Journal of experimental medicine2016
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome.
Trial report in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
173 citing papers in PubMed, 3 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus.Nature communications · 2025Pooled it
- Neuropathology of genetically defined malformations of cortical development-A systematic literature review.Neuropathology and applied neurobiology · 2021Pooled it
- A clinical score to guide in decision making for monogenic type I IFNopathies.Pediatric research · 2020Pooled it
- Imaging findings in pediatric interferonopathies.Pediatric radiology · 2026Review
- Familial pulmonary alveolar proteinosis and type I interferonopathy by mutation of STAT2 (TIMS2).The Journal of experimental medicine · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity.Reproduction & fertility · 2026Article
- ISGylation is disrupted byiScience · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- A transcriptomic microglia taxonomy across mouse and human pathologies.Nature immunology · 2026Article
- ISG15-USP18 signaling restrains viperin-dependent metabolic antiviral restriction.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms outpacing medicine in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Pharmacological inhibition of USP18 improves antibacterial responses and the intracellular control ofFrontiers in immunology · 2026Article
- Foetal disruptive brain injuries: Diagnosing the underlying pathogenetic mechanisms with cranial ultrasonography.Developmental medicine and child neurology · 2025Review
- The Chromosome 19 miRNA cluster guards trophoblasts against overacting innate immunity.Communications biology · 2025Article
- De novo pathogenic CSF1R variant implicates microglial dysfunction in pathogenesis of febrile infection-related epilepsy syndrome.Epilepsia · 2025Article
- Intronic branchpoint-to-acceptor variants underlying inborn errors of immunity.Journal of human immunity · 2025Article
- USP18 Deficiency Presenting as Severe Neonatal Encephalopathy: A Case Report and Review of Pseudo-TORCH Syndromes.Cureus · 2025Article
- Review
- DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.Biochemical Society transactions · 2025Article
113 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 7 institutions in 6 countries.
Funding
Abstract
Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.