title: CFTR transcription defects in pancreatic sufficient cystic fibrosis patients with only one mutation in the coding region of CFTR.
abstract: BACKGROUND
  Patients with cystic fibrosis (CF) manifest a multisystem disease due to deleterious mutations in each gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). However, the role of dysfunctional CFTR is uncertain in individuals with mild forms of CF (ie, pancreatic sufficiency) and mutation in only one CFTR gene.
  
  
  METHODS
  Eleven pancreatic sufficient (PS) CF patients with only one CFTR mutation identified after mutation screening (three patients), mutation scanning (four patients) or DNA sequencing (four patients) were studied. Bi-directional sequencing of the coding region of CFTR was performed in patients who had mutation screening or scanning. If a second CFTR mutation was not identified, CFTR mRNA transcripts from nasal epithelial cells were analysed to determine if any PS-CF patients harboured a second CFTR mutation that altered RNA expression.
  
  
  RESULTS
  Sequencing of the coding regions of CFTR identified a second deleterious mutation in five of the seven patients who previously had mutation screening or mutation scanning. Five of the remaining six patients with only one deleterious mutation identified in the coding region of one CFTR gene had a pathologic reduction in the amount of RNA transcribed from their other CFTR gene (8.4-16% of wild type).
  
  
  CONCLUSIONS
  These results show that sequencing of the coding region of CFTR followed by analysis of CFTR transcription could be a useful diagnostic approach to confirm that patients with mild forms of CF harbour deleterious alterations in both CFTR genes.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Molly B
authors.initials: MB
authors.lastname: Sheridan
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Hefferon
authors.forename: Nulang
authors.initials: N
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Merlo
authors.forename: Carlos
authors.initials: C
authors.lastname: Milla
authors.forename: Drucy
authors.initials: D
authors.lastname: Borowitz
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mogayzel
authors.forename: Garry R
authors.initials: GR
authors.lastname: Cutting
mesh_terms: D019943:Amino Acid Substitution; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator