Aggressive natural killer cell leukemia (ANKL) is a rare neoplasm characterized by the systemic infiltration of Epstein-Barr virus (EBV)-associated NK cells, and rapidly progressive clinical course. We report the case of a 45-year-old man with intellectual disability who developed ANKL, and describe the identification of a novel genetic mutation of coiled-coil domain-containing 22 (CCDC22). He presented with persistent fever, severe pancytopenia, and hepatosplenomegary. Following bone marrow aspiration, numerous hemophagocytes were identified. High EBV viral load was detected in NK cells fractionation by qPCR. The initial diagnosis was EBV-related hemophagocytic lymphohistiocytosis (EBV-HLH). A combination of immunosuppressive drugs and chemotherapy was administered, but was unsuccessful in controlling the disease. Therefore, he was treated with HLA-matched related allogeneic hematopoietic stem cell transplantation. However, his condition deteriorated within 30 days, resulting in fatal outcome. Autopsy revealed many EBV-infected NK cells infiltrating major organs, consistent with ANKL. Furthermore, whole-exome sequencing identified a novel missense mutation of the CCDC22 gene (c.112G>A, p.V38M), responsible for X-linked intellectual disability (XLID). CCDC22 has been shown to play a role in NF-κB activation. Our case suggests that CCDC22 mutation might be implicated in pathogenesis of EBV-HLH and NK-cell neoplasms as well as XLID via possibly affecting NF-κB signaling.

中文翻译：

---

在患有严重的爱泼斯坦-巴尔病毒相关的吞噬性淋巴细胞组织细胞增生症和侵袭性自然杀伤细胞白血病的患者中鉴定出新型CCDC22突变。

攻击性自然杀伤细胞白血病（ANKL）是一种罕见的肿瘤，其特征是与爱泼斯坦-巴尔病毒（EBV）相关的NK细胞全身浸润，并且临床进程迅速。我们报告了一名发展为ANKL的45岁智障男子的案例，并描述了含有卷曲螺旋结构域22（CCDC22）的新型遗传突变的鉴定。他表现出持续发烧，严重的全血细胞减少和肝脾肿大。骨髓抽吸后，鉴定出大量的噬血细胞。通过qPCR在NK细胞分级分离中检测到高EBV病毒载量。最初的诊断是EBV相关的吞噬淋巴细胞组织细胞增生症（EBV-HLH）。曾联合使用免疫抑制药物和化学疗法，但未能成功控制该疾病。因此，他接受了HLA匹配的相关异基因造血干细胞移植治疗。但是，他的病情在30天内恶化，导致致命的后果。尸检显示许多EBV感染的NK细胞浸润主要器官，与ANKL一致。此外，全外显子测序确定了CCDC22基因的新型错义突变（c.112G> A，p.V38M），其与X连锁智力障碍（XLID）有关。已经证明CCDC22在NF-κB激活中起作用。我们的案例表明，CCDC22突变可能通过影响NF-κB信号传导而参与EBV-HLH和NK细胞肿瘤以及XLID的发病机理。尸检显示许多EBV感染的NK细胞浸润主要器官，与ANKL一致。此外，全外显子测序确定了CCDC22基因的新型错义突变（c.112G> A，p.V38M），其与X连锁智力障碍（XLID）有关。已经证明CCDC22在NF-κB激活中起作用。我们的案例表明，CCDC22突变可能通过影响NF-κB信号传导而参与EBV-HLH和NK细胞肿瘤以及XLID的发病机理。尸检显示许多EBV感染的NK细胞浸润主要器官，与ANKL一致。此外，全外显子测序确定了CCDC22基因的新型错义突变（c.112G> A，p.V38M），其与X连锁智力障碍（XLID）有关。已经证明CCDC22在NF-κB激活中起作用。我们的案例表明，CCDC22突变可能通过影响NF-κB信号传导而参与EBV-HLH和NK细胞肿瘤以及XLID的发病机理。