Impaired CFTR function in mild cystic fibrosis associated with the S977F/T5TG12complex allele in trans with F508del mutation

J Cyst Fibros. 2013 Dec;12(6):821-5. doi: 10.1016/j.jcf.2012.12.014. Epub 2013 Jan 27.

Abstract

Background: The S977F mutation (c.2930C>T) in the CFTR gene (CFTR/ABCC7) is extremely rare. We describe the case of an adult patient carrying the complex allele S977F/T5TG12 in trans with the F508del mutation. Mild respiratory manifestations arose in adulthood associated with azoospermia, acute pancreatitis, minor hemoptysis and Cl(-) levels ranging from 40 to 42 mEq/L.

Method: Diagnosis was confirmed by repeated NPD measurements, genetic DHPLC analysis and a recently described functional assay measuring cAMP-dependent cell depolarization in peripheral blood monocytes.

Results: NPD measurements, DHPLC and monocyte functional assay (CF index=-18). Results were consistent with a CF phenotype.

Conclusions: The combined application of DHPLC and NPD analysis in the algorithm for CF diagnosis appears useful for the management of similar cases. In addition, the novel monocyte functional assay might contribute to improve our diagnostic capability, counseling and better treatment of these challenging clinical cases.

Keywords: Cystic fibrosis; Cystic fibrosis conductance transmembrane regulator; Mutation analysis; Nasal potential difference measurements.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Mutational Analysis
  • Humans
  • Male
  • Membrane Potentials
  • Nasal Mucosa / physiology

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator