RAG1基因新发突变1例分析及文献复习

Analysis of a new mutation of the RAG1 gene and literature review

目的探讨人重组激活基因1(RAG1)变异引起的联合免疫缺陷病(CID)患儿的临床、免疫特征及基因表型。方法对2020年3月佛山市妇幼保健院的1例CID患儿的临床资料进行分析并复习相关文献。结果该患儿因巨细胞病毒及耶氏肺孢子菌感染导致重症肺炎。血常规提示淋巴细胞减少,为(0.95~2.81)×10^(9)/L,CD3^(+)细胞、B细胞、免疫球蛋白水平明显低于同龄儿童。基因检测结果显示RAG1存在一处纯合子突变c.3074dupT(重复突变),导致氨基酸改变p.L1025Ffs*40(移码突变40位后蛋白翻译提前终止)。这个新型变异未被报道过。结论 CID患儿易被条件致病源引发严重感染;RAG1基因变异可致CID;新发现RAG1基因纯合子突变。

Objective To discuss the clinical, immune characteristics and gene-phenotype of children with combined immunodeficiency disease(CID) caused by mutation of human recombinant activating gene 1(RAG1).Methods The clinical data of a child with CID in Foshan maternal and child health hospital in March 2020 were analyzed and related literature was reviewed.Results The child had severe pneumonia due to cytomegalovirus and Pneumocystis yersinia infection.The routine blood test showed that lymphopenia [(0.95~2.81)×10^(9)/L],CD3^(+)cells, B cells and immunoglobulin were significantly lower than those of children of the same age.Gene detection showed that there was a homozygous mutation c.3074 dupT(repeated mutation) in RAG1,which resulted in the change of amino acid p.L1025 fs*40(protein translation was terminated earlier after frameshift mutation 40).This new mutation has not been reported in related clinical cases.Conclusion Children with CID are susceptible to severe infections caused by conditional pathogens, the mutation of the RAG1 gene can cause CID,and the homozygous mutation of the RAG1 gene is newly found.