Extensive molecular analysis of patients bearing CFTR-related disorders

J Mol Diagn. 2012 Jan;14(1):81-9. doi: 10.1016/j.jmoldx.2011.09.001. Epub 2011 Oct 20.


Cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs) may present with pancreatic sufficiency, normal sweat test results, and better outcome. The detection rate of mutations is lower in CFTR-RD than in classic CF: mutations may be located in genes encoding proteins that interact with CFTR or support channel activity. We tested the whole CFTR coding regions in 99 CFTR-RD patients, looking for gene mutations in solute carrier (SLC) 26A and in epithelial Na channel (ENaC) in 33 patients who had unidentified mutations. CFTR analysis revealed 28 mutations, some of which are rare. Of these mutations, RT-PCR demonstrated that the novel 1525-1delG impairs exon 10 splicing; by using minigene analysis, we excluded the splicing effect of three other novel intronic variants. Analysis of SLC26A genes revealed several variants, some of which are novel, that did not affect mRNA expression. Other mutations occurred in the ENaC genes encoding the ENaC subunits, but their frequency did not significantly differ between patients and controls. Our data, although obtained on a preliminary cohort of CFTR-RD patients, exclude a role of mutations in SLC26A and in SCNN genes in the pathogenesis of such disease; we confirm that CFTR analysis has a relevant role in CFTR-RD patients; and it appears mandatory to use CFTR scanning techniques and approaches to reveal the effect of novel mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anion Transport Proteins / genetics
  • Carrier Proteins / genetics
  • Case-Control Studies
  • Cells, Cultured
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Mutational Analysis
  • Epithelial Cells / metabolism
  • Epithelial Sodium Channels / genetics
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Mutation
  • Trypsin / genetics
  • Trypsin Inhibitor, Kazal Pancreatic


  • Anion Transport Proteins
  • Carrier Proteins
  • Epithelial Sodium Channels
  • SPINK1 protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic
  • PRSS1 protein, human
  • Trypsin