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DNA-BASED MUTATION ANALYSIS OF BRUTONS TYROSINE KINASE GENE IN PATIENTS WITH X-LINKED AGAMMAGLOBULINEMIA

VORECHOVSKY, I; Vihinen, Mauno LU ; DESAINTBASILE, G; HONSOVA, S; HAMMARSTROM, L; MULLER, S; NILSSON, L; FISCHER, A and SMITH, CIE (1995) In Human Molecular Genetics 4(1). p.51-58
Abstract
The identification of the BTK(Bruton's tyrosine kinase) gene defective in human immunoglobulin deficiency X-Iinked agammaglobulinaemia (XLA) and characterisation of BTK exon-intron boundaries has now allowed the analysis of mutations and polymorphisms at the level of genomic DNA, Using Southern blot analysis and the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, amplifying all 19 exons and the putative promoter region with a single annealling temperature, mutations have been identified in 19 out of 24 unrelated patients diagnosed as having XLA, Apart from a large deletion involving exon 19, nine missense (F25S, R288W, 1370M, M509V, R525P, N526K, R562W, A582V and G594R), two nonsense (E277X and R525X),... (More)
The identification of the BTK(Bruton's tyrosine kinase) gene defective in human immunoglobulin deficiency X-Iinked agammaglobulinaemia (XLA) and characterisation of BTK exon-intron boundaries has now allowed the analysis of mutations and polymorphisms at the level of genomic DNA, Using Southern blot analysis and the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, amplifying all 19 exons and the putative promoter region with a single annealling temperature, mutations have been identified in 19 out of 24 unrelated patients diagnosed as having XLA, Apart from a large deletion involving exon 19, nine missense (F25S, R288W, 1370M, M509V, R525P, N526K, R562W, A582V and G594R), two nonsense (E277X and R525X), five frameshift and two splice site mutations have been found affecting most coding exons and all major enzyme domains, No mutations or polymorphisms were detected in the putative promoter region, A single nucleotide deletion located in the last exon, resulting in a truncation of the eight C-terminal residues of Btk and a typical XLA phenotype, indicates structural and/or functional importance of Btk helix I in the catalytic domain, Although allelic heterogeneity at the BTK locus may partly explain clinical variability in families with XLA, compensatory and redundant mechanisms involved in B-cell development must play a role in the phenotypic diversity of the disease. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
4
issue
1
pages
51 - 58
publisher
Oxford University Press
external identifiers
  • wos:A1995QD37100008
  • scopus:0028851066
ISSN
0964-6906
language
English
LU publication?
no
id
27628fc8-f35d-4aab-8820-3749f4ff4a01 (old id 3853282)
date added to LUP
2013-06-28 14:39:00
date last changed
2017-07-30 03:41:33
@article{27628fc8-f35d-4aab-8820-3749f4ff4a01,
  abstract     = {The identification of the BTK(Bruton's tyrosine kinase) gene defective in human immunoglobulin deficiency X-Iinked agammaglobulinaemia (XLA) and characterisation of BTK exon-intron boundaries has now allowed the analysis of mutations and polymorphisms at the level of genomic DNA, Using Southern blot analysis and the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, amplifying all 19 exons and the putative promoter region with a single annealling temperature, mutations have been identified in 19 out of 24 unrelated patients diagnosed as having XLA, Apart from a large deletion involving exon 19, nine missense (F25S, R288W, 1370M, M509V, R525P, N526K, R562W, A582V and G594R), two nonsense (E277X and R525X), five frameshift and two splice site mutations have been found affecting most coding exons and all major enzyme domains, No mutations or polymorphisms were detected in the putative promoter region, A single nucleotide deletion located in the last exon, resulting in a truncation of the eight C-terminal residues of Btk and a typical XLA phenotype, indicates structural and/or functional importance of Btk helix I in the catalytic domain, Although allelic heterogeneity at the BTK locus may partly explain clinical variability in families with XLA, compensatory and redundant mechanisms involved in B-cell development must play a role in the phenotypic diversity of the disease.},
  author       = {VORECHOVSKY, I and Vihinen, Mauno and DESAINTBASILE, G and HONSOVA, S and HAMMARSTROM, L and MULLER, S and NILSSON, L and FISCHER, A and SMITH, CIE},
  issn         = {0964-6906},
  language     = {eng},
  number       = {1},
  pages        = {51--58},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {DNA-BASED MUTATION ANALYSIS OF BRUTONS TYROSINE KINASE GENE IN PATIENTS WITH X-LINKED AGAMMAGLOBULINEMIA},
  volume       = {4},
  year         = {1995},
}