| Literature DB >> 31940699 |
Fahad Alsohime1, Marta Martin-Fernandez1, Mohamad-Hani Temsah1, Majed Alabdulhafid1, Tom Le Voyer1, Malak Alghamdi1, Xueer Qiu1, Najla Alotaibi1, Areej Alkahtani1, Sofija Buta1, Emmanuelle Jouanguy1, Ayman Al-Eyadhy1, Conor Gruber1, Gamal M Hasan1, Fahad A Bashiri1, Rabih Halwani1, Hamdy H Hassan1, Saleh Al-Muhsen1, Nouf Alkhamis1, Zobaida Alsum1, Jean-Laurent Casanova1, Jacinta Bustamante1, Dusan Bogunovic1, Abdullah A Alangari1.
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.).Entities:
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Year: 2020 PMID： 31940699 PMCID： PMC7155173 DOI： 10.1056/NEJMoa1905633
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245