Pediatrics Department A, Soroka University Medical Center, Beer-Sheva, Israel; Immunology Clinic, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; The Primary Immunodeficiency Research Laboratory, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Clin Immunol. 2020 Apr;213:108366. doi: 10.1016/j.clim.2020.108366. Epub 2020 Feb 21.
The nuclease Artemis is a enzyme for V(D)J recombination allowing for the creation of T and B lymphocytes as well as for the repair of radiation-induced DNA double strand breaks encoded by the DCLRE1C gene. Artemis-null mutations are a known cause of severe combined immunodeficiencies (SCIDs) with radiosensitivity. Hypomorphic mutations in Artemis have been reported to cause a "leaky SCID"" phenotype, typically with hypogammaglobulinemia. We present four patients, all harboring the same unique hypomorphic mutation in the DCLRE1C gene, an 8-base pair insertion (c.1299_1306dup, p.Cys436*) presenting with a relatively mild phenotype including pulmonary infectious EBV-related lymphoproliferative diseases, an autoimmune phenomenon. Non-typical findings of IgG hypergammaglobulinemia accompanied by IgA and IgE deficiency were recorded in all patients. The typical viral, fungal, and opportunistic infections were absent, and patients reached a relatively old age.
核酸酶 Artemis 是 V(D)J 重组的一种酶，允许 T 和 B 淋巴细胞的产生，以及由 DCLRE1C 基因编码的辐射诱导的 DNA 双链断裂的修复。Artemis 缺失突变是一种已知的严重联合免疫缺陷（SCID）的原因，伴有辐射敏感性。Artemis 的功能降低突变已被报道导致“渗漏性 SCID”表型，通常伴有低丙种球蛋白血症。我们介绍了 4 名患者，他们都携带 DCLRE1C 基因中的同一独特的功能降低突变，即 8 个碱基对插入（c.1299_1306dup，p.Cys436*），表现出相对较轻的表型，包括与 EBV 相关的肺感染性淋巴组织增生性疾病和自身免疫现象。所有患者均记录到非典型 IgG 高丙种球蛋白血症伴 IgA 和 IgE 缺乏。典型的病毒、真菌和机会性感染不存在，患者达到相对较老的年龄。
