CFTR c.3874-4522A>G's impact on cystic fibrosis severity
Research type
Research Study
Full title
Investigating the possible association between expression of the CFTR: c.3874-4522A>G deep intronic variant and phenotype severity in patients with Cystic Fibrosis
IRAS ID
335624
Contact name
Deborah Morris-Rosendahl
Contact email
Sponsor organisation
Guy's and St Thomas' NHS Foundation Trust (GSTFT)
Duration of Study in the UK
1 years, 3 months, 25 days
Research summary
Cystic fibrosis is a condition affecting multiple systems in the body including the respiratory, digestive, and reproductive systems. Cystic fibrosis is inherited in a recessive manner, which means that only individuals with 2 mutations in the CFTR gene are affected.
Genetic testing in cystic fibrosis is used to establish a diagnosis in symptomatic individuals. Genes are made up of regions of DNA that include the instructions for how to make a protein; these are called coding regions. There are also regions of DNA within a gene that do not encode a protein, these are called non-coding regions. These regions occur in an alternating sequence throughout a gene and when changed, could create a mutation.
Non-coding regions have previously been overlooked for their role in disease, however we now know that mutations in these regions can cause disease. A mutation in the non-coding region of the CFTR gene, called c.3874-4522A>G has been detected in 22 patients in our laboratory and 20 individuals reported in the literature. This mutation causes disease by the inclusion of a section of non-coding DNA into the CFTR protein.
Large variation in disease severity has been reported in patients with this mutation and this may be due to variable expression levels of the mutant protein. This project aims to test the hypothesis that expression levels of the c.3874-4522A>G mutation are associated with severity of disease.
As the CFTR protein is expressed in nasal cells, this study involves taking nasal brushings from patients with the c.3874-4522A>G mutation. The level of expression of the c.3874-4522A>G mutation will be determined and compared to disease severity. This research may provide a greater insight into differences in disease severity in these patients.REC name
North of Scotland Research Ethics Committee 1
REC reference
24/NS/0033
Date of REC Opinion
15 Apr 2024
REC opinion
Further Information Favourable Opinion