Cystic Fibrosis
Background and Standard Service Information
The Molecular Genetics Division of the NCMG does not currently have the resources to take on testing previously carried out by the National Diagnostic Centre (NDC) at University College Galway. If you were previously using the NDC service, please do not send samples for cystic fibrosis testing to the NCMG. We will be working with the Department of Health and Children and the Eastern Regional Health Authority to resolve this regrettable situation. Meanwhile, we recommend that all former users of the National Diagnostic Centre testing service should send their samples to a laboratory accredited for molecular genetic testing. A useful list of laboratories can be found at www.cmgs.org. If you have any enquiries, please contact the Molecular Genetics laboratory.
Cystic fibrosis is an autosomal recessive disease, caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Mutations result in a wide phenotypic spectrum, from severe classical CF characterised by pancreatic insufficiency and chronic endobronchial infection, through to milder forms.
Other pathologies linked to mutations in the CFTR gene include CBAVD, liver disease, pancreatitis and desseminated bronchiectasis.
Essential referral information
In addition to supplying standard patient identification and referral information, the following should be clearly indicated:
- Patient’s symptoms (so we can be sure this is a diagnostic test).
- Any family history, including names, date of birth, relationship, genetic test results.
Forms to help you give us the information we need are available directly from the laboratory, or can be downloaded in either PDF or HTML format from the 'downloads' area to the right of the page.
Restrictions on testing
Carrier testing is limited to adults over the age of 16. Predictive testing for newborns is available only when both CF mutations in the family have been identified.
Tests offered
- Diagnostic test
- Diagnostic tests for patients with clinical symptoms suggestive of CF.
- Carrier detection
- Carrier detection for patients over the age of 16 with a family history of CF and/or a partner with the same.
- Prenatal diagnosis
- Prenatal diagnosis in cases where the mutations in both parents have been characterised.
- Predictive test
- Predictive testing for newborn babies when both CF mutations have been identified in the family.
Tests available include:
- Screen of the 11 ‘common’ Irish mutations:
F508del, R117H, I507del, G542X, G551D, R560T, N1303K, R352Q, 1717-1GA, 621+1GT and R553X. - Intron 8 poly T tract variant - Screened in CBAVD cases and when the R117H mutation has been identified.
Samples required
1-5ml blood in EDTA anticoagulant.
Sensitivity of tests
Estimated sensitivity of the routine 11 mutation CF screen is 92.5%.
Interpretation
Results are given in the form of an interpretative report.
- The presence of two mutations confirms a diagnosis of CF.
- Approximately 1% of true CF affecteds in the Irish population would be expected to give a negative result for the above 11 mutation screen. In these cases (and in cases where only one mutation has been identified), where CF is clinically indicated (eg positive sweat test), samples will be screened for the presence of rare mutations (see Further tests).
- The presence of one mutation in referrals for carrier status determination, confirms a carrier diagnosis for CF.
- The absence of all of the 11 Irish mutations in referrals for carrier status determination (in the absence of a family history of CF; or in the presence of a family history of CF, where the family mutations are included in the 11 mutation panel) reduces the risk of being a carrier from ~1/19 (Irish population risk) to less than 1%.
- Carrier results for a couple are reported as a joint report, and their risk of having an affected child is stated.
| Mother/Father | Affected | Carrier | 11 Irish mutations absent |
|---|---|---|---|
| Affected | 1 | 1/2 | ~ 1/500 |
| Carrier | 1/2 | 1/4 | ~ 1/1000 |
| 11 Irish mutations absent | ~ 1/500 | ~ 1/1000 | ~ 1/250000 |
- CBAVD
-
- All 11 Irish mutations absent: Presence of rare CF mutations is assumed in cases where CBAVD has been diagnosed.
- One mutation identified: As above.
- 5T/5T (interpretation is difficult, as this allele is present in 5% of the normal population). The 5T variant has been shown to be associated with CBAVD. Some studies suggest that the 5T variant may be a CF mutation in its own right, causing disease with partial penetrance.
- R117H/5T
-
- R117H is a mild mutation when inherited alongside a classical CF mutation, disease severity may be increased with the presence of 5T downstream.
Target reporting times
- Routine Diagnostic and Carrier tests:
- Indicative times for routine testing are listed on the Molecular Genetics section of the website.
- Urgent Diagnostic and Carrier tests:
- Verbal result available in 1-2 weeks.
- Prenatal diagnosis (CVS):
- Result available in 2 weeks.
- Prenatal diagnosis (Amniocentesis):
- Result available in 4 weeks.
Please Contact Us if you have not received a report within a week of your patient being due back in clinic.
Requests for copies of reports on the day that your patient is in clinic cannot normally be accommodated.
Further tests
In cases where there is a positive sweat test, but where both CF mutations have not been identified by the 11-mutation screen; samples can be added to a panel for analysis by dHPLC and sequencing.
This is a research collaboration with Professor Claude Ferec, Brest, France and results can take many months.
Our collaborative work in this area has recently been published.