Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille Calmette-Guérin infection

Five patients from 4 unrelated Tunisian families who presented with disseminated neonatal infection by Mycobacterium bovis bacille Calmette-Guérin strain were investigated. Two unrelated patients had different homozygous interleukin-12 receptor β1 subunit gene splice-site mutations (64+5G→A and 550-2A→G). Two siblings and 1 unrelated patient, all of whom were from the same town, carried the same mutation (297de18) within the interleukin-12p40 gene. This is the first description of familial cytokine deficiency reported so far. All patients had complete lack of expression of the affected polypeptide and a profound deficiency of in vitro interferon-γ production. The clinical severity of the mycobacterial infection was heterogeneous, even among affected members of the same family, which suggests the intervention of modifying genes.