Mutations in 21 different genes (IFNGR1, IFNGR2, IFNG, IL12RB1, IL12RB2, IL23R, IL12B, ISG15, USP18, ZNFX1, TBX21, STAT1, TYK2, IRF8, CYBB, JAK1, RORC, NEMO, SPPL2A, MCTS1, and IRF1) with more than 35 different genetic etiologies of MSMD have been described [12,13,14,15,16,17,18]. The gene discussed is ISG15; the disease is Mendelian susceptibility to mycobacterial diseases.