Genetic analysis of patients with defects in early B-cell development

Mary Ellen Conley, Arnon Broides, Vivian Hernandez-Trujillo, Vanessa Howard, Hirokazu Kanegane, Toshio Miyawaki, Sheila A. Shurtleff

Research output: Contribution to journalReview articlepeer-review

148 Scopus citations

Abstract

Approximately 85% of patients with defects in early B-cell development have X-linked agammaglobulinemia (XLA), a disorder caused by mutations in the cytoplasmic Bruton's tyrosine kinase (Btk). Although Btk is activated by cross-linking of a variety of cell-surface receptors, the most critical signal transduction pathway is the one initiated by the pre-B cell and B-cell antigen receptor complex. Mutations in Btk are highly diverse, and no single mutation accounts for more than 3% of patients. Although there is no strong genotype/phenotype correlation in XLA, the specific mutation in Btk is one of the factors that influences the severity of disease. Mutations in the components of the pre-B cell and B-cell antigen receptor complex account for an additional 5-7% of patients with defects in early B-cell development. Patients with defects in these proteins are clinically indistinguishable from those with XLA. However, they tend to be younger at the time of diagnosis, and whereas most patients with XLA have a small number of B cells in the peripheral circulation, these cells are not found in patients with defects in μ heavy chain or Igα. Polymorphic variants in the components of the pre-B cell and B-cell receptor complex, particularly μ heavy chain and λ5, may contribute to the severity of XLA.

Original languageEnglish
Pages (from-to)216-234
Number of pages19
JournalImmunological Reviews
Volume203
DOIs
StatePublished - 1 Feb 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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