Novel Mutation of Interferon-γ Receptor 1 Gene Presenting as Early Life Mycobacterial Bronchial Disease.

Maria J Gutierrez,Neelu Kalra,Gustavo Nino,Alexandra Horwitz

doi:10.1177/2324709616675463

Abstract

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a) Interferon-γ receptor deficiency can present resembling common disorders of the lung; (b) mycobacterial infections should be suspected when parenchymal lung disease, hilar lymphadenopathy, and endobronchial disease are present; and (c) high index of suspicion for immunodeficiency should be maintained in patients with disseminated nontubercular mycobacterial infection.

Highlights

Interferon-γ receptor 1 (IFNGR1) deficiency is a rare immune deficiency characterized by selective susceptibility to mycobacterial disease caused by genetic mutations in the IFNGR1 gene.[1]
On IFNγ binding, IFNGR1 chain induces the assembly of the IFN-γ receptor with subsequent activation of constitutively associated Janus kinases 1 and 2 (Jak1/2) and the downstream signal transducer and activator of transcription 1 (STAT 1) mediated gene transcription.[5]
We describe the case of a toddler boy with a history of recurrent wheezing found to have an invasive endobronchial mycobacterial infection

Summary

Introduction

Interferon-γ receptor 1 (IFNGR1) deficiency is a rare immune deficiency characterized by selective susceptibility to mycobacterial disease caused by genetic mutations in the IFNGR1 gene.[1]. Complete autosomal recessive IFNGR1 deficiency is characterized by early onset of disseminated life-threatening infections by lowvirulent mycobacteria, lack of response to IFN-γ cytokine replacement therapy, and high mortality.[6,7] To date hematopoietic stem cell transplant is the only curative therapy available for these patients.[6] the clinical phenotype of the autosomal recessive partial and autosomal dominant forms is milder, usually with later onset, less severe

Results

Conclusion