title: Transcriptional regulatory defects in the first intron of Bruton's tyrosine kinase.
abstract: BACKGROUND
  X-linked agammaglobulinemia (XLA), characterized by the early onset of recurrent bacterial infections, profound hypogammaglobulinemia, and a markedly diminished number of peripheral B lymphocytes, is caused by mutations in the Bruton's tyrosine kinase (BTK) gene. The >600 unique mutations identified to date include single base pair substitutions, small insertions or deletions, and gross deletions. A few cases, however, have been found to have no mutations in the coding region even with reduced BTK mRNA or protein expression. Mutations in intron 1 positions +5 (G-->A) and +6 (T-->G) of the BTK gene have been identified, and these changes were associated with reduced transcriptional activity.
  
  
  METHODS
  In the present study a novel mutation in intron 1 position +5 (G-->T) was identified in a Japanese patient with XLA. The reporter constructs containing these mutations were made, and the reporter activities were measured using a luciferase assay.
  
  
  RESULTS
  All the mutant constructs were demonstrated to have reduced transcriptional activity.
  
  
  CONCLUSIONS
  Positions +5 and +6 in intron 1 of the BTK gene are critical for transcriptional activity, and defects in these regions cause XLA.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejon, Korea.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.forename: Meina
authors.initials: M
authors.lastname: Zhao
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamagishi
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics*; D001402:B-Lymphocytes / Q000201:enzymology; D041321:Chromosomes, Human, X; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human