干扰素γ受体1缺陷患儿的临床特征及功能、基因分析

Clinical features,gene function and molecular analysis of one child with IFN-γreceptor 1 deficiency

目的探讨1例疑似孟德尔遗传易感分枝杆菌病（Mendelian susceptibility to mycobacterial disease,MSMD）患儿的临床特征,检测IL-12/23-IFN-γ通路的完整性,并进行IFN-γ受体1（IFNGR1）基因分析。方法根据患儿的临床表现及常规的免疫学筛查试验排除常见原发性免疫缺陷病,Q-RT-PCR在mRNA水平检测患儿及健康对照者IL-12/23-IFN-γ通路的完整性,通过PCR及RT-PCR分别对患儿及其父母的IFNGR1基因进行扩增并测序。结果患儿有播散性卡介苗（BCG）病及全身多系统损害的表现。患儿全血经BCG和IFN-γ共同刺激48 h后IL-12B的表达水平与单独BCG刺激后比较明显降低（P〈0.05）;基因测序发现患儿IFNGR1第6外显子818-821位杂合缺失4个碱基（c.818-821 del TTAA）,使第276位脯氨酸突变为终止密码（p.Asn274fsX276）,父母此位点正常。结论 MSMD患儿临床特征为BCG病及全身多系统损害。Q-RT-PCR检测IL-12/23-IFN-γ通路完整性是一种有效的筛查MSMD的手段;IFNGR1突变是引起本例患儿发生上述临床特征的根本原因。

Objective To explore the clinical features,detect the function of the IL-12/23-IFN-γ axis and identify the IFN-γ receptor 1（IFNGR1） gene mutation in a child with suspected Mendelian susceptibility to mycobacterial disease（ MSMD）. Methods Firstly,we ruled out the common primary immunodeficiency disease（PID） based on the clinical manifestation and screening tests of immune function,and then detected the integrity of the IL-12 /23-IFN-γ axis by Q-RT-PCR. IFNGR1 gene was sequenced according to the results of Q-RT-PCR. Results The child suffered from disseminated BCG disease and multi-system lesions. The production of IL-12 B in response to BCG plus IFN-γ was reduced,compared with stimulation by BCG alone（P〈 0.05）. A heterozygous deletion mutation was found at the position of 818 to 821（c.818-821 del TTAA）in exon 6 of IFNGR1 gene that resulted in proline at the position of 276 changing into the stop codon（p. Asn274fsX276） in the patient. In contrast,IFNGR1 genes were normal in her parents. Conclusion MSMD Chidren have the clinical feature of disseminated BCG disease and multi-system lesions. Detecting the function of IL-12 /23-IFN-γ axis is an effective tool for the screening of MSMD. IFNGR1 genetic mutation is responsible for BCG infections and multi-system lesions in this child.