Fevang Børre, Fagerli Unn Merete, Sorte Hanne, Aarset Harald, Hov Håkon, Langmyr Marit, Keil Thomas Morten, Bjørge Ellen, Aukrust Pål, Stray-Pedersen Asbjørg, Gedde-Dahl Tobias
K.G. Jebsen Center for Cancer Immunotherapy and K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Case Reports Immunol. 2018 May 14;2018:2053716. doi: 10.1155/2018/2053716. eCollection 2018.
The nuclease Artemis is essential for the development of T-cell and B-cell receptors and repair of DNA double-strand breaks, and a loss of expression or function will lead to a radiosensitive severe combined immunodeficiency with no functional T-cells or B-cells (T-B-SCID). Hypomorphic mutations in the gene can lead to a functional, but reduced, T-cell and B-cell repertoire with a more indolent clinical course called "leaky" SCID. Here, we present the case of a young man who had increasingly aggressive lymphoproliferative skin lesions from 2 years of age which developed into multiple EBV+ B-cell lymphomas, where a hypomorphic mutation in the gene was found in a diagnostic race against time using whole exome sequencing. The patient was given a haploidentical stem cell transplant while in remission for his lymphomas and although the initial course was successful, he succumbed to a serious pneumonia 5 months after the transplant. The case underscores the importance of next-generation sequencing in the diagnosis of patients with suspected severe immunodeficiency.
核酸酶Artemis对于T细胞和B细胞受体的发育以及DNA双链断裂的修复至关重要，其表达或功能丧失会导致一种对辐射敏感的严重联合免疫缺陷，即不存在功能性T细胞或B细胞（T-B-SCID）。该基因的次等位基因突变可导致功能性但数量减少的T细胞和B细胞库，临床病程较为隐匿，称为“渗漏型”SCID。在此，我们报告一例年轻男性病例，该患者从2岁起出现侵袭性不断增加的皮肤淋巴细胞增生性病变，进而发展为多发性EBV阳性B细胞淋巴瘤，通过全外显子组测序在与时间赛跑的诊断过程中发现了该基因的次等位基因突变。患者在淋巴瘤缓解期接受了单倍体相合干细胞移植，尽管初始过程成功，但移植后5个月因严重肺炎死亡。该病例强调了下一代测序在疑似严重免疫缺陷患者诊断中的重要性。
