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Genetic testing for cystic fibrosis (CF) and CFTR-related disorders (R184 / R185 / R253)

Background information

CFTR-related disorders include cystic fibrosis (CF) and congenital bilateral absence of the vas deferens (CBAVD). Subsets of patients with isolated pancreatitis or bronchiectasis also have variants in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. There are >1600 mutations known, which occur throughout the 27 exons of the CFTR gene.

The frequencies of these mutations vary between ethnic groups.

Cystic fibrosis is an autosomal recessive disorder of epithelial tissue, with widespread dysfunction of exocrine glands leading to defective chloride transport across membranes and a lack of water in external secretions, excess mucus production in the respiratory and gastrointestinal tracts and protein plugs in the pancreas. Pulmonary disease is the major cause of morbidity and mortality in CF and meconium ileus occurs at birth in 15-20 percent of individuals with CF.

CBAVD (congenital bilateral absence of the vas deferens) can occur in affected men without pulmonary or gastrointestinal manifestations of CF - these men have azoospermia and are thus infertile. This is classed as a CFTR-related disorder rather than cystic fibrosis due to the lack of classical symptoms.

The incidence of disease varies between ethnic origins - in the white British population, ~1/2500 individuals are affected and ~1/25 are carriers.

Testing strategy

Clinically affected probands

R184.1 Targeted mutation testing

R184.2 CFTR gene sequencing

R184.3 MLPA

R253.1 Newborn screening follow-up (four most common variants). All neonates are offered testing for cystic fibrosis by means of an immunoreactive trypsin (IRT) test at five days of age. All individuals with a raised IRT are tested for four common cystic fibrosis mutations.

For more information, visit:

NHS newborn blood spot (NBS) screening programme: detailed information

Targeted analysis for known / previously reported familial variants

R185.1 Carrier testing for:

Individuals with a family history of CF (up to 4th degree relative)
Partners of known carriers (R246)
Both parents of a fetus with an echogenic bowel
Close consanguineous couples (e.g 1st cousins) and from an ethnic group with a high carrier frequency
Prospective egg or sperm donors

R240.1 + R321.1 Prenatal testing and maternal cell contamination where both parents have previously been identified as carriers.

Testing strategy

Fluorescent multiplex PCR (CFTR Devyser Assay) that targets 53 of the most common CFTR mutations in the UK and European population. The assay can be modified to enable simultaneous analysis of the intron 8 polyT and TG variants if appropriate.

If requested, further testing includes:

MLPA: a dosage based analysis for the detection of deletions and duplications of one or more of the 27 coding exons of the CFTR gene (accounting for approximately 2 percent of CFTR variants)
Sequencing of the CFTR gene to detect rare variants which is undertaken by the West Midlands Regional Genetics Laboratory

Turnaround times for genetic / genomic testing

Specimen requirements and referring samples

Requesting specialties: