2例Omenn综合症患儿临床、免疫学特征及基因突变分析

Clinical and immunological characteristics as well as mutation analysis of two children with Omenn syndrome

目的 Omenn综合征是由于RAG1或RAG2基因突变导致的,本研究是为了寻找RAG基因的新发突变,提高临床工作者对本病的了解,以减少漏诊与延迟诊断。方法对2012年在重庆医科大学附属儿童医院收治的2例疑似严重联合免疫缺陷(severe combined immunodeficiency,SCID)的患儿及患儿父母收集血标本进行RAG1/RAG2基因PCR扩增、PCR产物的双向序列测定、TCR Vβ亚家族克隆谱型分析、TREC含量检测。结果 2例患儿均有Omenn综合症典型临床表现和T+B-NK+免疫学表型,均为RAG1基因复合杂合性突变,其中例1的1个基因突变(3073insA,G1025L)被确认为新发突变,其余3个基因突变(1180 C>T,A394T;1806T>G;C602T;1949A>G,A650S)均被报道过。患儿的大多数TCR Vβ亚家族表现为单克隆或寡克隆峰,患儿TREC含量明显低于正常人TREC含量。结论例1患儿的1个RAG1基因突变(3073insA,G1025L)被确认为新发突变,从而扩展了RAG1基因突变谱。部分Omenn综合症患儿存在漏诊与延迟诊断,因此提高临床工作者对本病的认识对于早期诊断至关重要。Omenn综合症主要治疗方式为干细胞移植,早期诊断并且迅速干细胞移植可能可以降低死亡率。

Omenn syndrome has been found to be caused by mutations in RAG1 or RAG2 gene. This study is to seek novel mutation in RAG gene, and improve the clinical doctors＇ understangding of this disease, in order to reduce the possibility of misdiagnosis and delayed diagnosis. This study enrolled 2 cases of suspected severe combined immunodeficiency （SCID） from Children＇s Hospital of Chongqing Medical University in 2012. Firstly, we collected blood samples from children and their parents for RAG1/RAG2 genes PCR amplification. Then the PCR product was used for forward and reverse sequencing, TCR ~~ analysis, as well as TREC content determination. We found that the 2 cases had typical clinical manifestations of Omenn syndrome and T^B-NK＋ phenotype, and both of them are compound heterozygosity mutations in RAG1 gene. Furthermore, one novel mutation （3073insA, G1025L） was identified, while the other three mutations （ll80C〉T, A394T; 1806T〉G, C602T; 1949A〉G, A650S） have been reported before. Most of the 24 TCR V[3 subfamilies presented monoclonal or oligoelonal peaks in case 1. And TREC content of patients was lower than that of normal individuals clearly. In conclusion, one novel mutation （3073insA, G1025L） was identified in this study, which could expand the RAG1 gene mutation spectrum. Our result may also contribute to early diagnosis of Omenn syndrome, whieh is extremely important for Omenn syndrome treatment.