Cystic Fibrosis (CF) is the most common life-threatening autosomal recessive condition in Caucasians. It is due to mutations within the CF Transmembrane Conductance Regulator (CFTR) gene on chromosome 7.
Mutations affect sodium and chloride transport across cell membranes and as a result cause production of thickened secretions within airways and ducts.
In the UK, the incidence is 1 in 2500. The condition is less common in those of Asian and African ancestry.
There are many different mutations identified within the CFTR gene. The commonest mutation is the ΔF508 mutation (70%). In the UK, the CF carrier rate, for one CF mutation, is 1 in 20 to 1 in 25, with a recurrence risk of 1 in 4 in each pregnancy for parents who are both carriers.
Who to carrier test?
Carrier testing can be considered in the following circumstances:
- The partner of someone who is either affected with CF or who is a CF carrier if this may influence their reproductive choices.
- Any adult first degree family member of someone who is at least a carrier of cystic fibrosis.
- You can send blood to carrier test a pregnant woman with a family history/partner family history of CF, but please concurrently refer to clinical genetics (as stated below) and mark the test on the blood form as ‘urgent’.
Siblings of a child with CF, or a CF carrier, will not be screened until old enough to understand the implications of the test.
How to test
- 2 to 4ml blood in EDTA (anticoagulant) tube sent with DNA request card to Northern Molecular Genetic Service via your local hospital pathology department.
- Include reasons for testing or name of affected relative on sample referral form where applicable.
By completing the form, this indicates that patients have consented to testing, and DNA being stored by the testing laboratory.
Who to refer to clinical genetics
In the following circumstances, please refer to clinical genetics:
- Couples in a consanguineous relationship (1st cousins or closer).
- Pregnant women with a family history/partner family history of CF (please mark as urgent).
- When test results show that both partners are carriers of CF.
- When test results show that one partner is affected with CF and the other is a carrier.
Interpretation of results
The laboratory report will contain information to help guide the risk assessment and any further management. Please also refer to the following table.
| Result | Interpretation and management |
|---|---|
| No mutation present | The report should state a small residual risk of the patient being a carrier, based on the family history information provided and their ethnicity. Testing of their partner is not indicated. |
| Heterozygote for a CFTR mutation | Carrier of CF. If they are of reproductive age we advise carrier testing for their partner. Other relatives may wish to seek advice around testing (eg. siblings, adult children, parents). |
| Two CFTR mutations detected (homozygote or compound heterozygote). | Likely to be affected with CF or a CFTR-related disorder. Further testing and/or onward referral may be suggested (for example to the CF unit, respiratory medicine and/or fertility). If they are of reproductive age we advise carrier testing for their partner. Other relatives may wish to seek advice around testing. |
