What is the purpose of a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene test?

From the Guidelines

Genetic testing for cystic fibrosis is strongly recommended for individuals with symptoms suggestive of the disease, those with a family history, and for reproductive planning in couples with known carrier status, as it enables prompt treatment initiation and can significantly improve quality of life and extend lifespan. The test analyzes the CFTR gene for mutations, with the most common being the F508del mutation, and typically involves a blood sample or buccal swab sent to a specialized laboratory for DNA analysis 1. Results usually take 2-4 weeks to process, and the test can identify carriers, diagnose CF, or determine if someone is not affected. According to the Cystic Fibrosis Foundation evidence-based guideline for the management of CRMS/CFSPID, genetic testing is recommended for people with CRMS/CFSPID who have <2 disease-causing variants identified by NBS, and should undergo CFTR sequencing including intronic regions 1.

Key Points to Consider

• Genetic counseling is strongly advised before and after testing to understand implications of results
• CF genetic testing is highly accurate but may not detect all possible mutations, as over 2,000 CFTR mutations exist
• Early diagnosis through genetic testing enables prompt treatment initiation, which can significantly improve quality of life and extend lifespan
• The CFF recommends thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening, and repeat sweat testing until at least age 8 1

Recommendations for Clinical Practice

• Genetic testing should be offered to individuals with symptoms suggestive of CF, those with a family history of the disease, and for reproductive planning in couples with known carrier status
• Genetic counseling should be part of the care of CRMS/CFSPID, depending on the needs of that individual and family
• HCPs providing genetic counseling should have training and/or clinical expertise in CF and genetics, and a licensed or certified GC should be accessible to families of people with CRMS/CFSPID 1

From the Research

Cystic Fibrosis Gene Test

• Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein 2, 3, 4.
• The CFTR gene is located on chromosome 7 and plays a crucial role in regulating chloride ion flow, with its absence or malfunction causing the production of thick mucus that affects several organs 4.
• There are over 2000 identified mutations in the CFTR gene, which are classified into seven categories based on their dysfunction mechanisms 4.
• The diagnosis of CF can be established by evaluation of CFTR function with a sweat chloride test, and the latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project should be used to aid in diagnosis 5.

CFTR Modulator Therapy

• CFTR modulator therapy is a pivotal approach utilized for the management of cystic fibrosis, and has revolutionized CF care by targeting the underlying defect in CF that causes decreased CFTR protein synthesis, function, or stability 2, 3, 6.
• The therapy has been shown to have a substantial positive impact on the lives of individuals with CF, with benefits including improved lung function, reduced pulmonary exacerbations, and improved nutrition and quality of life 6.
• However, the efficacy and tolerability of CFTR modulator therapy in individuals with advanced CF lung disease need to be monitored, and its impact on lung disease progression and the need for lung transplantation require further evaluation 2, 6.

Genetic Testing

• Genetic testing can be used to identify mutations in the CFTR gene, and can aid in the diagnosis of CF 3, 5.
• The identification of the CFTR gene in 1989 gave hopes of rapidly finding a cure for the disease, and recent approaches have enabled the identification of small molecules targeting either the CFTR protein directly or its key processing steps 3.
• The future of CFTR-targeted treatment lies in combinatory therapies that will enable CF patients to receive a customized treatment 3.