Identification of Btk mutations in 20 unrelated patients with X-Iinked agammaglobulinaemia (XLA)

Jin, H., Webster, A.D.B., Vihinen, M., Sideras, P., Vorechovsky, l., Hammarstróm, L., Bernatowska-Matuszkiewicz, E., Smith, C.I.E., Bobrow, M. and Vetrie, D. (1995) Identification of Btk mutations in 20 unrelated patients with X-Iinked agammaglobulinaemia (XLA). Human Molecular Genetics, 4(4), pp. 693-700. (doi: 10.1093/hmg/4.4.693) (PMID:7633420)

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 mis match 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 (R641 H) 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.

• Item Type: Articles
• Status: Published
• Refereed: No
• Glasgow Author(s) Enlighten ID: Vetrie, Professor David
• Authors: Jin, H., Webster, A.D.B., Vihinen, M., Sideras, P., Vorechovsky, l., Hammarstróm, L., Bernatowska-Matuszkiewicz, E., Smith, C.I.E., Bobrow, M., and Vetrie, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Human Molecular Genetics
• Publisher: Oxford University Press
• ISSN: 0964-6906
• ISSN (Online): 1460-2083