A Point Mutation in the SH2 Domain of Bruton's Tyrosine Kinase in Atypical X-Linked Agammaglobulinemia

X-Linked Agammaglobulinemia is the prototypical humoral immunodeficiency first described by Bruton in 19521. It is characterized by a paucity of circulating B cells and a drastic reduction in the serum concentrations of immunoglobulins2,3. Studies analyzing patterns of X chromosome inactivation showed that the genetic defect was intrinsic to the B-cell lineage,4 and mapping studies located the defect in the midportion of the long arm of the X chromosome at Xq225–7. Recently, two reports demonstrated that mutations of the cytoplasmic tyrosine kinase gene Btk (the gene for Bruton's tyrosine kinase, previously designated bpk or atk) are . . .