Abstract:

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.