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IDENTIFICATION OF BTK MUTATIONS IN 20 UNRELATED PATIENTS WITH X-LINKED AGAMMAGLOBULINEMIA (XLA)

JIN, H; WEBSTER, ADB; Vihinen, Mauno LU ; SIDERAS, P; VORECHOVSKY, I; HAMMARSTROM, L; BERNATOWSKAMATUSZKIEWICZ, E; SMITH, CIE; BOBROW, M and VETRIE, D (1995) In Human Molecular Genetics 4(4). p.693-700
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
4
issue
4
pages
693 - 700
publisher
Oxford University Press
external identifiers
  • wos:A1995QV81400029
  • scopus:0028949513
ISSN
0964-6906
DOI
10.1093/hmg/4.4.693
language
English
LU publication?
no
id
0194b9db-0ed6-43cf-ae29-58cc74fafa3a (old id 3853226)
date added to LUP
2013-06-28 14:38:23
date last changed
2017-07-30 03:31:39
@article{0194b9db-0ed6-43cf-ae29-58cc74fafa3a,
  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.},
  author       = {JIN, H and WEBSTER, ADB and Vihinen, Mauno and SIDERAS, P and VORECHOVSKY, I and HAMMARSTROM, L and BERNATOWSKAMATUSZKIEWICZ, E and SMITH, CIE and BOBROW, M and VETRIE, D},
  issn         = {0964-6906},
  language     = {eng},
  number       = {4},
  pages        = {693--700},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {IDENTIFICATION OF BTK MUTATIONS IN 20 UNRELATED PATIENTS WITH X-LINKED AGAMMAGLOBULINEMIA (XLA)},
  url          = {http://dx.doi.org/10.1093/hmg/4.4.693},
  volume       = {4},
  year         = {1995},
}