title: Identification of Btk mutations in 20 unrelated patients with X-linked agammaglobulinaemia (XLA).
abstract: X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency resulting from mutations in the gene for a cytoplasmic protein tyrosine kinase (Btk). We have utilised reverse-transcription-based PCR in combination with the chemical cleavage and mismatch technique (CCM) to screen for Btk mutations in 42 unrelated patients having classical XLA or 'leaky' XLA-like phenotypes. A variety of mutations, including point mutations, large deletions and splicing defects were detected using this strategy. In total, 20 mutations were found in these patients. All the mutations were different with the exception of three unrelated patients who all showed the same Arg-->His amino acid substitution (R641H) at a highly-conserved residue in the kinase domain. We have also used structural modelling of the Btk kinase domain to predict how two different amino acid substitution mutations at highly-conserved residues are likely to affect the Btk kinase activity.
authors.affiliation: Division of Medical and Molecular Genetics, UMDS of Guy's Hospital, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
authors.forename: P
authors.initials: P
authors.lastname: Sideras
authors.forename: I
authors.initials: I
authors.lastname: Vorechovsky
authors.forename: L
authors.initials: L
authors.lastname: Hammarstróm
authors.forename: E
authors.initials: E
authors.lastname: Bernatowska-Matuszkiewicz
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Bobrow
authors.forename: D
authors.initials: D
authors.lastname: Vetrie
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D000596:Amino Acids / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013728:Terminator Regions, Genetic; D014960:X Chromosome
chemical_list: D000596:Amino Acids; D017931:DNA Primers; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human