Cystic Fibrosis

Background Information

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.

Standard service

Essential referral information

In addition to supplying standard patient identification and referral information, the following should be clearly indicated:

  1. Patient's symptoms (so we can be sure this is a diagnostic test).
  2. Any family history, including names, date of birth, relationship, genetic test results.

Patient information request forms to help you give us the information we need are available directly from the laboratory or can be downloaded here in PDF format: Cystic Fibrosis PIR.

^^

Restrictions on testing

  1. Carrier testing is limited to adults over the age of 16.
  2. Predictive testing for newborns is available only when both CF mutations in the family have been identified.
^^

Tests offered

  1. Diagnostic tests for patients with clinical symptoms suggestive of CF.
  2. Carrier detection for patients over the age of 16 with a family history of CF and/or a partner with the same.
  3. Prenatal diagnosis - in cases where the mutations in both parents have been characterised.
  4. Predictive testing for newborn babies when both CF mutations have been identified in the family.
  5. Information on CF testing for male infertility is also available.

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 CF screen: 92.5% for the 11 mutation screen.

^^

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.
Couple’s risk of having an affected child.
Parent 1
Parent 2		 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
^^

Target reporting times

  • Diagnostic and carrier tests (Routine): Indicative times for routine testing are listed on the Molecular Genetics section of the website.
  • Diagnostic and carrier tests (urgent): Verbal result available in 1-2 weeks.
  • Prenatal diagnosis (CVS): 2 weeks.
  • Prenatal diagnosis (Amniocentesis): 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.

^^