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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 To investigate the clinical features of mycobacterial susceptibility (MSMD) mutation caused by IFNGR1 gene mutation. Methods The clinical features of 2 patients with MSMD gene mutation in IFNGR1 gene were analyzed. The release of interferon - γ (IFN - γ) was detected by ELISA. The expression of IFNGR1 protein was detected by flow cytometry. The mutation of IFNGR1 was analyzed by Sanger sequencing. Results (1) Two cases of BCG disease occurred within 3 months after birth, the initial manifestation of axillary lymph node enlargement on the BCG vaccination side, and gradually spread to the lung, intestine, central and bone marrow. The diagnosed age was 4 years old and 6 years old respectively. There were no defects in the assessment of routine immune function (lymphocyte subsets, immunoglobulins, neutrophil respiratory burst function and complement). (2) 2 cases of children with significantly lower release of IFN-γ, IFNGR1 protein expression were lower than normal. (3) There was a homozygous mutation of c.665 G> A (p.G219R) in 1 case, both parents were c.665 G> A (p.G219R) heterozygous mutation; 1 case had c.665 G> A p.G219R) and c.310 C> A (p.A104N), which were inherited from the c.665G> A (p.G219R) heterozygous mutation in the children and the father [c.310C > A (p. A104N) heterozygous mutation]. One case of children with mutations in the new mutation, no prior literature. (4) 2 cases of children before the diagnosis of anti-tuberculosis treatment ineffective, diagnosed with IFN-γ, BCG infection was controlled, no other adverse reactions. Conclusion IFNGR1 gene mutation can lead to MSMD. In routine immunization of children with BCG, there is no defect to consider, the disease may be considered, related protein testing, IFN-γ release experiments and genetic analysis contribute to the diagnosis. IFN-γ treatment has a certain effect.