title: Mutations of the Btk gene in 12 unrelated families with X-linked agammaglobulinemia in Japan.
abstract: Alterations of the Bruton's tyrosine kinase (Btk) gene are responsible for X-linked agammaglobulinemia (XLA). Although mutations in various regions were reported mainly in the Caucasian population, correlation between the locations of mutation and the clinical phenotypes remains unclear. We report 12 abnormalities of the Btk gene found in 12 unrelated families out of 14 XLA families in Japan and their clinical features. We utilized Southern blotting and single-strand conformation polymorphism (SSCP) analysis. Gene rearrangement in the kinase domain was identified in two patients by Southern blotting. Seven point mutations, two small deletions, and one small insertion were detected by SSCP and sequencing. The SSCP analysis also provided information about the carriers in these families. We found some clinical heterogeneity in the affected family members with the same gene mutation. Moreover, there is considerable inconsistency between the locations of gene aberrations and the immunological phenotypes. Some patients with a nonsense mutation, which may result in the lack of kinase domain, have detectable B cells and immunoglobulins. These identified alterations will provide valuable clues to the Btk protein function and the pathogenesis of XLA.
authors.affiliation: Department of Pediatrics, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Iwasaki
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Naritaka
authors.forename: Y
authors.initials: Y
authors.lastname: Kono
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D001483:Base Sequence; D008040:Genetic Linkage; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D014960:X Chromosome
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human