IFNGR1基因突变致分枝杆菌易感性疾病2例病例报告  

Two Mendelian susceptibility to mycobacterial diseases patients with novel IFNGR1 gene mutations

作　　者：应文静[1] 刘丹如[1] 孙金峤[1] 王文婕[1] 俞晔珩[1] 王晓川[1] 

机构地区：[1]复旦大学附属儿科医院临床免疫科,上海201102

出　　处：《中国循证儿科杂志》2017年第4期295-299,共5页Chinese Journal of Evidence Based Pediatrics

基　　金：上海市科学技术委员会西医引导项目:14411965400

摘　　要：目的探讨IFNGR1基因突变致分枝杆菌易感性疾病(MSMD)的临床特征。方法总结2例IFNGR1基因突变MSMD患儿的临床特征,ELISA方法检测干扰素-γ(IFN-γ)释放功能,流式细胞术检测IFNGR1蛋白表达,Sanger测序方法分析IFNGR1基因突变。结果 (1)2例患儿均生后3月龄内出现卡介苗病,以卡介苗接种侧腋下淋巴结肿大为初始表现,并逐渐播散累及肺部、肠道、中枢和骨髓。确诊年龄分别为4岁和6岁。常规免疫功能(淋巴细胞亚群、免疫球蛋白、中性粒细胞呼吸爆发功能和补体)评估未见缺陷。(2)2例患儿的IFN-γ释放能力明显低下、IFNGR1蛋白表达均低于正常。(3)1例存在c.665 G>A(p.G219R)纯合突变,其父母均为c.665 G>A(p.G219R)杂合突变;1例存在c.665 G>A(p.G219R)和c.310 C>A(p.A104N)复合杂合突变,分别遗传自患儿母亲[c.665 G>A(p.G219R)杂合突变]及父亲[c.310 C>A(p.A104N)杂合突变]。其中1例患儿的突变为新发突变,既往无文献报道。(4)2例患儿在确诊前抗痨治疗效果不佳,确诊后加用IFN-γ,卡介苗感染得到控制,未见其他不良反应。结论 IFNGR1基因突变可导致MSMD。卡介苗病患儿常规免疫评估无缺陷时,需考虑该病可能,相关蛋白检测、IFN-γ释放实验和基因分析有助于诊断。IFN-γ治疗有一定疗效。Objective： In this study, two Mendelian susceptibility to mycobacterial diseases （MSMD） patients with novel IFNGR1 mutation were reported. Methods： Clinical manifestations of two patients with IFNGR1 mutation were reviewed. The IFN-γ level was analyzed by ELISA, the IFNGR1protein was detected by flow cytometry. Mutation analysis in IFNGR1 was performed by Sanger sequencing.Results： ①Clinical manifestations： In 2 patients, BCG disease was found during 3 months after birth, and the draining lymphadenectasis after BCG vaccination was the onset feature. The BCG infection was gradually disseminated to lung, intestinal tract, central nervous system and bone. The diagnosing age of the 2 patients was 4 and 6 years old, respectively. Routine immune function evaluation （lymphocyte subgroup, immunoglobulin, DHR analysis, complement） was normal. ②The two patients showed significantly lower IFN-γ concentrations in the supernatant after stimulation with medium alone, and IFN-γ concentrations did not significantly increase after stimulation with LPS or with LPS plus IL-12. ③IFNGR1 protein was very low in the two patients. ④Gene sequencing： Case 1 had a c.665G〉A （p.G219R） homozygous mutation, whose parents were both with c.665G〉A （p.G219R） heterozygotes mutation. Case 2 had c.665G〉A （p.G219R） and c.310 C〉A （p.A104N） compound heterozygous mutation, and her mother had c.665G〉A （p.G219R） heterozygous mutation and her father had c.310 C〉A （p.A104N） heterozygous mutation. The mutation A104N was novel. ⑤Treatment： Both patients were suffered recurrent mycobacteria infection before diagnosis. While treated with IFN-γ after diagnosis, the BCG infection was controlled without any adverse reactions.Conclusion： IFNGR1 gene mutation can cause MSMD. When the routine immunological evaluation of patients with BCG disease is normal, it is necessary to consider the possibility of MSMD. The detection of protein and gene analysis are helpful to the diagnosis of the disease.

关 键 词：分枝杆菌易感性疾病 IFWGR1基因 卡介苗病 

分 类 号：R725.9[医药卫生—儿科]