title: Novel insertions of Bruton tyrosine kinase in patients with X-linked agammaglobulinemia.
abstract: Mutations in the gene encoding Bruton tyrosine kinase (BTK) result in X-linked agammaglobulinemia (XLA), an immunodeficiency of antibody defect. By using base excision sequence scanning method (BESS) followed by direct sequencing we found in seven unrelated families with a classical XLA phenotype various mutations including six novel mutations (g.64512_64513insC, c.108_109insG, c.1700_1701insACTACAG, g.51375_51376GC>TG, g.63991_63992insGGTAGAAAAAA, c.1956_1957insCA) and a previously known silent polymorphism (c.2031C>T). Except for two mutations, the alterations affect the kinase domain. There was exceptionally high proportion of insertions in the cohort. Frameshift insertion was found altogether in five patients, three of which are on introns, one in upstream region, and one in exon 18 leading to frameshift mutation and truncation of the protein. In the intron 4 there is a substitution of two bases. Carrier detection was performed in four families. In one case the mutation was found to be de novo.
authors.affiliation: Institute of Medical Technology, FIN-33014 University of Tampere, Finland.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Okoh
authors.forename: Leena
authors.initials: L
authors.lastname: Kainulainen
authors.forename: Kaarina
authors.initials: K
authors.lastname: Heiskanen
authors.forename: M Nizam
authors.initials: MN
authors.lastname: Isa
authors.forename: Kim
authors.initials: K
authors.lastname: Varming
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: Mauno
authors.initials: M
authors.lastname: Vihinen
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D017809:Fatal Outcome; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human