INTRODUCTION AND OBJECTIVES Severe combined immunodeficiency (SCID) is a subset of primary immunodeficiency diseases caused by a hereditary deficiency of the adaptive immune system. Mutation in recombination activating gene (RAG) is known as the underlying genetic cause of SCID. RAG protein plays a pivotal role in V(D)J recombination which is the main process to assemble lymphocyte antigen receptors during T- and B-cell development. The patients are characterized by recurrent infections, failure to thrive, chronic diarrhea, and fever, in early infancy. Herein, we present a case of SCID with rare neurological manifestations affected by a mutation in RAG1. PATIENTS AND METHODS The patient was a 15-month-old infant born to a consanguineous family. She was presented with neurological abnormalities including facial nerve palsy, seizure, and decreased consciousness. Next-generation sequencing (NGS)-based primary immunodeficiency disease (PID)-gene panel screen and Sanger sequencing were performed to identify the genetic mutation. RESULTS We found a novel homozygous missense mutation in RAG1, c.1210C>T,p.Arg404Trp, which was predicted to be deleterious (combined annotation dependent depletion, CADD score of 27.4). Both parents were heterozygous carriers for this mutation. According to her laboratory data, both T cell and B cell numbers were decreased and the patient was diagnosed as RAG1- SCID. CONCLUSIONS SCID is a pediatric emergency with a variety of manifestations in infants. Therefore, accurate diagnosis importantly in the case of rare manifestations must be considered in these patients. Our findings point toward the importance of genetic assessment for early diagnosis and timely treatment of this disorder.

中文翻译：

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一种新的纯合 RAG1 突变与严重的联合免疫缺陷和神经系统表现有关。

引言和目标 严重联合免疫缺陷 (SCID) 是由遗传性适应性免疫系统缺陷引起的原发性免疫缺陷疾病的一个子集。重组激活基因（RAG）的突变被认为是SCID的潜在遗传原因。RAG 蛋白在 V(D)J 重组中起关键作用，这是在 T 细胞和 B 细胞发育过程中组装淋巴细胞抗原受体的主要过程。患者的特点是在婴儿早期反复感染、发育迟缓、慢性腹泻和发烧。在此，我们提出了一例受 RAG1 突变影响的罕见神经系统表现的 SCID 病例。患者和方法 患者是一个 15 个月大的婴儿，出生于一个近亲家庭。她出现了神经系统异常，包括面神经麻痹、癫痫发作、和意识下降。进行了基于下一代测序 (NGS) 的原发性免疫缺陷病 (PID) 基因面板筛选和 Sanger 测序以识别基因突变。结果 我们在 RAG1 中发现了一个新的纯合错义突变，c.1210C>T,p.Arg404Trp，预计它是有害的（结合注释依赖性缺失，CADD 评分为 27.4）。父母双方都是这种突变的杂合子携带者。根据她的实验室数据，T细胞和B细胞数量均减少，患者被诊断为RAG1-SCID。结论 SCID 是一种儿科急症，在婴儿中具有多种表现。因此，在这些患者中必须考虑在罕见表现的情况下进行准确诊断。