重组活化因子1基因突变所致不同临床表型严重联合免疫缺陷病3例分析

Variable clinical phenotypes of severe combined immunodeficiency caused by RAG1 mutations

目的总结分析重组活化因子(RAG)1基因突变所致严重联合免疫缺陷病(SCID)的不同临床及免疫特点。方法 2012年9月至2013年4月首都医科大学附属北京儿童医院收治的3例SCID患儿,经RAG1基因突变分析获得明确诊断,经HLA配型方法除外母体T淋巴细胞经胎盘输注,经细胞遗传学方法判断淋巴细胞增殖功能。结果病例1表型为经典SCID,病例2表型为Omenn综合征,病例3为伴反复自身免疫性溶血性贫血的非典型SCID。RAG1基因突变分析结果,病例1复合杂合位点1:1870 C>T,Arg624Cys;位点2:2005 G>A,Glu669Lys。位点1为已报道突变,位点2为新发现的错义突变。病例2复合杂合位点1:994 C>T,Arg332X;位点2:1439 G>A,Ser480Asn。均为新发现突变。病例3纯合2095 C>T,R699W,为已报道突变。前两例患儿均于自动出院后不久夭折,后者仍处于反复住院治疗自身免疫性溶血性贫血过程中。结论 RAG1突变所致SCID临床表现有差异,经典SCID和Omenn综合征预后严重,需移植治疗。

Objective To investigate the different clinical and immune features of variable phenotypes of severe combined immunodeficiency caused by RAG 1 mutations.Methods From 2012.9 to 2013.04, three patients were included in the study, and records of clinical details were reviewed. Results The phenotypes of three patients were typical SCID for patient 1, Omenn syndrome for patient 2 and atypical SCID complicated with recurrent autoimmune hemolytic anemia for patients 3, respectively.RAG 1 mutations were compound heterozygous allele 1 ： 1870 C 〉 T/Arg624Cys, allele 2 ： 2005 G 〉 A/Glu669Lys （allele l was published mutation, allele 2 was de novel mutation） for patient 1 ; compound heterozygous allele 1 ： 994 C 〉 T/ Arg332X, allele 2：1439 G 〉 A/Ser480Asn （both mutations were de novel mutations）for patient 2 ;homozygous 2095 C 〉 T/ R699W for patient 3 and was published mutation. First two patients died soon after discharge.Patient 3 was treated for recurrent autoimmune hemolytic anemia in our ward.Conclusion RAG1 mutations can lead to variable SCID phenotypes.Patients with typical SCID and Omenn syndrome were with poor prognosis ,which need transplantation treatment.