Abstract：
Autosomal recessive tyrosine kinase 2 (TYK2) deficiency is characterized by susceptibility to mycobacterial and viral infections. Here, we report a 4-year-old female with severe respiratory viral infections, EBV-driven Burkitt-like lymphoma, and infection with the neurotropic Jamestown Canyon virus. A novel, homozygous c.745C > T (p.R249*) variant was found in TYK2. The deleterious effects of the TYK2 lesion were confirmed by immunoblotting; by evaluating functional responses to IFN-α/β, IL-10, and IL-23; and by assessing its scaffolding effect on the cell surface expression of cytokine receptor subunits. The effects of the mutation could not be pharmacologically circumvented in vitro, suggesting that alternative modalities, such as hematopoietic stem cell transplantation or gene therapy, may be needed. We characterize the first patient from Canada with a novel homozygous mutation in TYK2.
摘要：
常染色体隐性酪氨酸激酶2（TYK2）缺乏症的特征是对分枝杆菌和病毒感染的易感性。这里,我们报告了一名4岁女性患有严重的呼吸道病毒感染，EBV驱动的Burkitt样淋巴瘤,感染嗜神经詹姆斯敦峡谷病毒.一部小说,纯合c.745C>T（p。在TYK2中发现了R249*)变体。通过免疫印迹证实了TYK2病变的有害作用；通过评估对IFN-α/β的功能反应，IL-10和IL-23;并通过评估其对细胞因子受体亚基的细胞表面表达的支架作用。该突变的影响在体外无法在药理学上规避，这表明替代模式，如造血干细胞移植或基因治疗，可能需要。我们描述了第一位来自加拿大的患者在TYK2中具有新的纯合突变。
