IFNGR1 variants associated with mycobacterial infections were extensively studied by Dorman et al.
The aim of our study was to search for IFNGR1 variants by sequencing all exons, in a cohort of Polish patients with osteoarticular lesions.
IFNGR1 is highly conserved, and it is possible to estimate the probability of finding a non-deleterious variant at random from the IFNGR1 entry in the ExAC browser .
It is of some significance that our study, with all exons of IFNGR1 sequenced, did not find any other low-frequency variant previously associated with mycobacterial infection.
It is, therefore, of some importance that screening groups do not narrow the search for IFNGR1 low-frequency variants prematurely where cost allows (e.
Of importance here is that, in this study, all dominant partial cases were heterozygous for IFNGR1 low-frequency variants c.
15], in which the IFN-[gamma]-responsive cell line THP-1 was transduced with IFNGR1 gene variant p.
27] recommended that, along with genetic counseling, "undetectable or low levels of IFN-[gamma] should lead to the child being treated with subcutaneous IFN-[gamma] while searching for mild low-frequency variants of IFNGR1 and IFNGR2, or null low-frequency variants of IL12B and IL12RB1".
The cause of mycobacterial osteoarticular infection in most patients in this study could not be explained by exonic low-frequency variants of IFNGR1, and therefore, the other genes mentioned earlier should also be analyzed in order to evaluate further mechanisms for susceptibility to mycobacterial osteoarticular infections.
This is the first missense exonic splice variant to be found and also is the first time that mycobacterial osteomyelitis has been found together with an IFNGR1 missense variant in dominant mode.
Lack of other low-frequency variants found with all exons of IFNGR1 sequenced, in the screen of patients with osteoarticular lesions, indicates that screening should not yet be restricted to those IFNGR1 exons, in which deleterious low-frequency variants have so far been found; plus other genes involved in Type 1 T-helper-cell-mediated immune inflammation should also be analyzed.