Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia

Yuko Ohta, Robert N. Haire, Ronda T. Litman, Shu Man Fu, Robert P. Nelson, Jamie Kratz, Stephen J. Kornfeld, Maite De La Morena, Robert A. Good, Gary W. Litman

Research output: Contribution to journalArticle

101 Scopus citations


X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC, a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5′ untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.

Original languageEnglish (US)
Pages (from-to)9062-9066
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - Sep 13 1994



  • DNA sequencing
  • Missense mutation
  • PCR
  • Primary immunodeficiency disease
  • Protein-tyrosine kinase

ASJC Scopus subject areas

  • General

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