Mendelian Susceptibility to Mycobacterial Disease

Atypical Pneumonia – An Uncommon Presentation of a Well-Known Disease

“…None of the symptoms, signs or risk factors [5][6][7] that would classically increase the index of suspicion was present in this patient (e.g., persistent productive cough, night sweats, weight loss, upper lobe infiltrates, cavitation, miliary pattern, social deprivation, old age and compromised immunity). Additionally, she had no close personal or professional contact with TB, nor was there a family history of this affliction.…”

Gene Association Studies in Tuberculosis: A Question of Case-Control Definitions?

“…The discovery of a large number of single nucleotide polymorphisms (SNPs) in the human genome [4] has revived interest in TB genetic association studies [5]. IFN-γ gene knockout studies in the experimental mouse model [6][7]and the identification of extreme phenotypes in TB patients (Mendelian Susceptibility to Mycobacterial Diseases ) associated with mutations in the IFN-γ/IL-12/IL-23 pathway [8][9][10] indicated IFN-γ to be a key player in immunity to TB [11]. However, studies with functional SNPs in the IFN-γ gene [12][13][14][15][16] have shown highly variable and sometimes opposing effects of the same SNPs in different ethnic populations [17][18][19].…”

Clinical Genetics for the Pulmonologist: Introduction

“…For example, Mendelian susceptibility to mycobacterial respiratory infections is a fascinating area of research. Mutations of the genes participating in the interleukin-12 (IL-12), IL-23, and especially interferon-␥ response pathways may increase the susceptibility to disseminated and potentially fatal forms of mycobacterial infection (including infections with poorly pathogenic mycobacteria such as the Bacille Calmette-Guérin) in the absence of any other identified immune deficiency [27][28][29][30][31] . This nicely illustrates how genetics may intrude into fields of medicine hitherto thought to be entirely dependent upon exogenous agents (such as infectious diseases).…”