title: Genetic analysis of patients with defects in early B-cell development.
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 micro heavy chain or Igalpha. Polymorphic variants in the components of the pre-B cell and B-cell receptor complex, particularly micro heavy chain and lambda5, may contribute to the severity of XLA.
authors.affiliation: Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN 38105, USA. maryellen.conley@stjude.org
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
authors.forename: Arnon
authors.initials: A
authors.lastname: Broides
authors.forename: Vivian
authors.initials: V
authors.lastname: Hernandez-Trujillo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Howard
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Shurtleff
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human