Mutation analysis of the Bruton's tyrosine kinase gene in X-linked agammaglobulinemia: identification of a mutation which affects the same codon as is altered in immunodeficient xid mice

Hum Mol Genet. 1994 Jan;3(1):161-6. doi: 10.1093/hmg/3.1.161.


X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency disease in man, reflecting an arrest in differentiation of pre-B cells to mature B cell stages. The gene defective in XLA has been identified as a cytoplasmic protein tyrosine kinase, named btk (Bruton's tyrosine kinase). Here we report the characterization of mutations in the btk gene of five unrelated XLA families. Amplified products were generated from cDNA, cloned and sequenced. Three single point mutations and two small insertions were identified. One of the point mutations and the two insertions created stop codons that would lead to truncated btk proteins. In one XLA patient we found a single basepair substitution that altered the highly conserved Arg288 within the SH2 domain and would therefore abrogate interactions with substrate phosphotyrosines. In another XLA patient a single basepair substitution was observed that altered the conserved Arg28 residue in the N-terminal unique region of unknown function. This residue is also mutated in the xid mouse, which has a different, less severe, B cell deficiency. We conclude that a similar mutation in the btk gene leads in man to an almost complete arrest at an early stage of B cell differentiation, but in the mouse to only limited B cell abnormalities.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / enzymology
  • Agammaglobulinemia / genetics*
  • Agammaglobulinemia / immunology
  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Blotting, Northern
  • Blotting, Southern
  • Cell Differentiation
  • Codon / genetics
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Mutational Analysis*
  • DNA Primers
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Immunologic Deficiency Syndromes / genetics*
  • Infant
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases / genetics*
  • X Chromosome*


  • Codon
  • DNA Primers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • DNA
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse

Associated data

  • GENBANK/S69983