Normal function of the cystic fibrosis conductance regulator protein can be associated with homozygous (Delta)F508 mutation

Pediatr Res. 2002 Nov;52(5):628-35. doi: 10.1203/00006450-200211000-00005.


Cystic fibrosis (CF) is caused by mutations of the gene encoding for the CFTR (CF transmembrane conductance regulator) protein. The most frequent mutation, the (Delta)F508 mutation, results in a defective cAMP-regulated chloride transport in the epithelial cells. The spectrum of clinical manifestations in patients bearing homozygous (Delta)F508 mutations can vary considerably, suggesting that, in the patients with a mild disease, CFTR could be partly functional. To test this hypothesis, we explored in nasal ciliated epithelial cells (NCC) of 9 control subjects and 23 (Delta)F508 homozygous patients the anion conductive pathway by a halide sensitive fluorescent dye assay SPQ (6-methoxy-N-3'-sulfopropylquinolinium) and the CFTR transcript levels by RT-PCR. As 50% represented the lowest fraction of the control subjects NCC demonstrating a cAMP-dependent conductance, a CF patient was considered as "cAMP responder" if at least 50% of the NCC tested displayed a cAMP-dependent conductive pathway. According to these criteria, 8 of the 23 patients were considered as cAMP responders. They had a significantly less severe disease considering the respiratory function and infectious status. The amount of CFTR mRNA did not differ between the control subjects and the patients. No statistical correlation could be found between the transcript level and the expression of a cAMP conductive pathway. This cAMP-dependent Cl(-) conductance detected in homozygous NCC could be due to a residual CFTR activity and may explain the mild phenotypes observed in some (Delta)F508 homozygous patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlorides / metabolism*
  • Codon / genetics
  • Cyclic AMP / physiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / deficiency
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Epithelial Cells / metabolism
  • Fluorescent Dyes / metabolism
  • Homozygote
  • Humans
  • Ion Transport / genetics*
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • Phenotype
  • Point Mutation*
  • Quinolinium Compounds / metabolism
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Second Messenger Systems
  • Sequence Deletion*


  • CFTR protein, human
  • Chlorides
  • Codon
  • Fluorescent Dyes
  • Quinolinium Compounds
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 6-methoxy-N-(3-sulfopropyl)quinolinium
  • Cyclic AMP