Transcript analysis of CFTR nonsense mutations in lymphocytes and nasal epithelial cells from cystic fibrosis patients

Hum Mutat. 1995;5(3):210-20. doi: 10.1002/humu.1380050305.


The mutational effects at the mRNA level were investigated by RT-PCR analysis of nine different nonsense mutations (Q39X, E60X, R75X, G542X, L719X, Y1092X, R1162X, S1196X, W1282X) and one frameshift mutation (1078delT) within the CFTR gene. With the exception of mutation R1162X, reduced mRNA levels ranging from 30% to less than 5% of the wild type have been observed. In case of the R75X and E60X mutations, the mRNA reduction was accompanied by the appearance of atypical CFTR isoforms. Single exon 3 skipping, as well as joint exon 2 and 3 skipping, was observed in lymphocyte and nasal epithelial mRNA derived from R75X alleles. The analysis of mRNA transcribed from E60X alleles revealed skipping of exon 3 (lymphocytes and nasal epithelial cells) or skipping of exons 3 and 4 (nasal epithelial cells). With the exception of the E60X mutation, no obvious tissue-specific differences in the splicing pattern and ratios of mutation to wild-type transcripts were detected between lymphocytes and nasal epithelial cells. In addition to aberrant splicing, the reduction of transcripts is the most common effect of nonsense and frameshift mutations within the CFTR gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelium / metabolism
  • Exons
  • Female
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation*
  • Nasal Mucosa / metabolism
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics*
  • Transcription, Genetic


  • CFTR protein, human
  • Membrane Proteins
  • Oligonucleotide Probes
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator