Related Experiment Video
Updated: Jun 20, 2026
Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein Expressed in Saccharomyces cerevisiae
Published on: May 10, 2014
Clinical and molecular characterization of S1118F-CFTR
Himabindu Penmatsa1, Carla A Frederick, Sunitha Nekkalapu
1Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Insights
The S1118F-CFTR mutation impairs cystic fibrosis transmembrane conductance regulator (CFTR) maturation, leading to atypical CF symptoms. Correctors can improve CFTR function in individuals with this mutation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Cystic fibrosis (CF) is a severe autosomal recessive disorder.
- It typically presents with lung disease, pancreatic insufficiency, and elevated sweat chloride levels.
Observation:
- A patient with meconium ileus and pancreatic sufficiency presented with compound heterozygous mutations DeltaF508/I1027T and S1118F.
- Intermediate sweat chloride levels were observed in this patient.
Findings:
- The S1118F-CFTR mutation results in <15% mature CFTR (band C) and ~10-15% of wild-type (WT) CFTR function.
- mRNA levels for S1118F-CFTR and WT-CFTR are comparable, indicating impaired protein maturation.
- CFTR-correcting therapies can enhance mature and functional S1118F-CFTR by 3-4 fold.
Implications:
- The S1118F-CFTR mutation causes a distinct CF phenotype with atypical symptoms.
- Understanding the molecular basis of S1118F-CFTR is crucial for developing targeted CF therapies.
- This research highlights the potential of CFTR modulators for patients with specific CFTR mutations.
Background:
Cystic fibrosis is a lethal autosomal recessive disorder usually associated with lung disease, pancreatic insufficiency and high sweat chloride levels.
Clinical Case:
A patient admitted to Le Bonheur Children's Medical Center (LBCMC, Memphis, TN) showed symptoms of meconium ileus which required exploratory laparotomy, bowel resection and ileostomy. Genotyping showed DeltaF508/I1027T on one chromosome and S1118F on the other. Sweat testing on three different occasions gave negative and intermediate results (22.7, 24.6 mmol/L; 55.1, 58.6 mmol/L and 55.1, 58 mmol/L) and pancreatic elastase testing showed normal levels.
Objective:
To characterize S1118F-CFTR mutation at a molecular level to help understand the associated CF-phenotype.
Methods:
Molecular characterization of S1118F-CFTR mutant was studied in HEK-293 cells at 37 degrees C. Various biochemical methods such as Western blotting, real-time PCR, Pulse chase labeling and iodide efflux assay were employed.
Results:
S1118F-CFTR makes less than 10-15% of mature CFTR (band C) compared to WT-CFTR. The mRNA levels of S1118F-CFTR and WT-CFTR are comparable. S1118F-CFTR is functional but shows about 10-15% of WT-CFTR activity. S1118F-CFTR shows impaired maturation and CF-correctors can increase the amount of mature and functional CFTR by three- to fourfold.
Conclusion:
S1118F-CFTR shows impaired maturation and an individual with S1118F-CFTR paired with DeltaF508-CFTR exhibits atypical CF symptoms with intermediate sweat chloride level and meconium ileus despite documented pancreatic sufficiency.
More Related Videos
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:24Cystic Fibrosis: Management
Sinus disease and chronic sinusitis...