BTK and agammaglobulinemia: The first genetic etiology of agammaglobulinemia (i.e., early-onset immunodeficiency, repeated hospitalization for severe life-threatening bacterial infections, <1% peripheral blood B cells, severe reduction of all serum Ig) was identified in 1993 as variants in BTK, an X-linked gene (Tsukada et al., 1993; Vetrie et al., 1993; Fig. 3).