JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency.
N Engl J Med
; 382(3): 256-265, 2020 01 16.
Article
em En
| MEDLINE
| ID: mdl-31940699
ABSTRACT
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.).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Interleucinas
/
Interferons
/
Ubiquitina Tiolesterase
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Janus Quinase 1
/
Doenças Hereditárias Autoinflamatórias
/
Inibidores de Janus Quinases
/
Mutação com Perda de Função
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2020
Tipo de documento:
Article