title: Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia.
abstract: Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result in premature termination of the translation product. Mutations were detected in most BTK exons with a predominance of frameshift and nonsense mutations in the 5' end of the gene and missense mutations in its 3' part, corresponding to the catalytic domain of the enzyme. Nonsense and frameshift mutations were associated with diminished levels of BTK mRNA expression, except for a frameshift mutation in exon 17 and two nonsense mutations in exon 2, indicating that these cases are not confined to penultimate exons. One amino acid substitution (R28H) was found in the pleckstrin homology domain's residue, which is mutated in mice bearing the X-linked immunodeficiency phenotype; another substitution (R307G) was identified in the src homology domain 2. All remaining amino acid substitutions were found in the catalytic domain of Btk.
authors.affiliation: Karolinska Institute, Department of Biosciences, NOVUM, Huddinge, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Vorechovský
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: J M
authors.initials: JM
authors.lastname: Hertz
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: T
authors.initials: T
authors.lastname: Klemola
authors.forename: M
authors.initials: M
authors.lastname: Fiorini
authors.forename: I
authors.initials: I
authors.lastname: Quinti
authors.forename: R
authors.initials: R
authors.lastname: Paganelli
authors.forename: H
authors.initials: H
authors.lastname: Ozsahin
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D017668:Age of Onset; D000483:Alleles; D015152:Blotting, Northern; D002384:Catalysis; D002648:Child; D002675:Child, Preschool; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse