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.).

中文翻译：

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JAK 抑制剂治疗患有遗传性 USP18 缺乏症的儿童。


泛素特异性肽酶 18 (USP18) 缺乏是一种严重的 I 型干扰素病。 USP18 通过阻断 Janus 相关激酶 1 (JAK1) 与 I 型干扰素受体的接触来下调 I 型干扰素信号传导。 USP18 的缺失会导致干扰素介导的炎症未得到缓解，并且在围产期是致命的。我们描述了一名患有脑积水、坏死性蜂窝组织炎、全身炎症和呼吸衰竭的新生儿。外显子组测序在 USP18 的一个重要剪接位点发现了纯合突变。编码的蛋白质被表达，但缺乏负调节能力。使用鲁索替尼治疗后，患者迅速持续康复。 （由沙特国王大学等资助）。