Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis

Ada Hamosh, Bruce C. Trapnell, Pamela L. Zeitlin, Chahrzad Montrose-Rafizadeh, Beryl J. Rosenstein, Ronald Crystal, Garry R. Cutting

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Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two African-American patients with nonsense mutations in each CF gene and severe pancreatic disease, but mild pulmonary disease. In order to examine the effect of these nonsense mutations on CF gene expression, bronchial and nasal epithelial cells were obtained from one of these patients (no. 246), a compound heterozygote for nonsense mutations R553X and W1316X; a healthy normal individual; a patient (no. 528) homozygous for the common CF mutation (ΔF508); and a CF patient (no. 272) who carries the R553X mutation and a mis-sense mutation, S549N. When mRNA from bronchial cells of the normal individual, the ΔF508 homozygote, and the S549N/R553X compound heterozygote was reverse transcribed and amplified by polymerase chain reaction using primers derived from the CF gene, DNA fragments of the predicted size were observed. However, patient no. 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) messenger RNA, and therefore should have severely diminished, and possibly absent, CFTR protein. Furthermore, < 2% of the CFTR transcripts in nasal epithelial cells from patient no. 272 (S549N/R553X) were derived from the gene with the nonsense mutation. We conclude that severe reduction in CFTR mRNA causes CF, but can have different consequences in the lung and pancreas.

Original languageEnglish
Pages (from-to)1880-1885
Number of pages6
JournalJournal of Clinical Investigation
Issue number6
Publication statusPublished - 1 Jan 1991
Externally publishedYes



  • Allele-specific oligonucleotides
  • Genotype
  • Phenotype
  • Polymerase chain reaction
  • Reverse transcription

ASJC Scopus subject areas

  • Medicine(all)

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