Abstract：
BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented.
METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control.
RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation.
CONCLUSIONS: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient\'s quality of life.
METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control.
RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation.
CONCLUSIONS: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient\'s quality of life.
摘要：
背景：Artemis缺乏症是一种常染色体隐性遗传疾病，其特征是具有细胞放射敏感性增加的联合免疫缺陷。在这次审查中,本文介绍了15例DCLRE1C变异患者的临床和遗传特征.
方法：人口统计，临床,免疫学,我们回顾性收集了2013年至2023年间确诊的DCLRE1C变异患者的遗传特征.通过彗星试验评估了三名患者的放射敏感性，与年龄和性别匹配的健康对照相比。
结果：7名在生命的前6个月有严重感染的患者被诊断为T-B-NK+SCID（严重联合免疫缺陷）。其中,四个人接受了移植，其中一人死于早期移植后并发症。8例患者有副形态变异。其中一半在等待合适的捐赠者，而另一半已经进行了移植。大多数患者出生在近亲家庭（93.3％）。大多数患者反复鼻肺感染（73.3%），一名患者在诊断前除急性呼吸道感染外没有其他感染。两名患者（13.3％）以自身免疫性溶血性贫血的形式出现了自身免疫。仅在一名患者中观察到生长迟缓（6.6％），在中位(IQR)21.5(12-45)个月的随访期间,存活的11例患者未发现恶性肿瘤.三名有新变异的患者表现出放射敏感性增加和DNA修复受损，提供恶性转化的潜在脆弱性。
结论：早期诊断，避免辐射,精心准备移植有助于减少并发症，提高预期寿命，提高患者的生活质量。
方法：人口统计，临床,免疫学,我们回顾性收集了2013年至2023年间确诊的DCLRE1C变异患者的遗传特征.通过彗星试验评估了三名患者的放射敏感性，与年龄和性别匹配的健康对照相比。
结果：7名在生命的前6个月有严重感染的患者被诊断为T-B-NK+SCID（严重联合免疫缺陷）。其中,四个人接受了移植，其中一人死于早期移植后并发症。8例患者有副形态变异。其中一半在等待合适的捐赠者，而另一半已经进行了移植。大多数患者出生在近亲家庭（93.3％）。大多数患者反复鼻肺感染（73.3%），一名患者在诊断前除急性呼吸道感染外没有其他感染。两名患者（13.3％）以自身免疫性溶血性贫血的形式出现了自身免疫。仅在一名患者中观察到生长迟缓（6.6％），在中位(IQR)21.5(12-45)个月的随访期间,存活的11例患者未发现恶性肿瘤.三名有新变异的患者表现出放射敏感性增加和DNA修复受损，提供恶性转化的潜在脆弱性。
结论：早期诊断，避免辐射,精心准备移植有助于减少并发症，提高预期寿命，提高患者的生活质量。
