JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency.
PMID 31940699 | PMCID PMC7155173 | DOI 10.1056/NEJMoa1905633 · The New England journal of medicine · 2020
Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery. (Funded by King Saud University and others.).
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | USP18 | “JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency.” | 0.98 | hgnc_dict_v1 |
| gene | JAK1 | “USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor.” | 0.98 | hgnc_dict_v1 |