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Home Service Laboratory Services Clinical Genetics Service Patients who are UNLIKELY to benefit from a referral to Clinical Genetics Cystic Fibrosis

Cystic Fibrosis

Cystic fibrosis (CF) has an estimated prevalence of ~1 in 3,000.  The most common associated complications are chronic lung disease, exocrine pancreatic insufficiency and male infertility.  CF is an autosomal recessive disorder.  It is estimated that ~1 in 20 of us are carriers of CF.  Being a carrier of CF is not expected to have any implications for your health, but it may have reproductive implications.

We do not see patients for CF carrier testing in the Genetics clinic, unless there are additional issues.  Where both partners are found to be carriers of CF, the couple can be referred to Clinical Genetics to discuss reproductive options.

Non-genetic specialists (including GPs) can request CF carrier testing (5-10ml EDTA sample, sent to the Genetics lab).  It is imperative to state the name and details of the patient’s known affected relative. Click here for the Test request form.   Non-healthcare professionals are not permitted to request genetic testing.

Please see below for more detailed information on CF and understanding results.  This information is also available as a leaflet.

  • What is cystic fibrosis and the CFTR gene?

    Cystic fibrosis (CF) is a complex condition, which can affect many parts of the body.  The most common associated complications are recurring lung infections and chronic lung disease, pancreatic insufficiency (e.g. diabetes mellitus), difficulty gaining weight, chronic gastrointestinal symptoms and male infertility.

    Almost every cell in our body contains DNA.  DNA provides the instructions for how our cells should work.  A gene is a length of DNA which codes for the production of a particular protein.  If this code is disrupted by a genetic variant (“spelling mistake”) this can affect the function of the protein, and cause health problems.

    CF is caused by having a genetic variant (“spelling mistake”) in both copies of your CFTR gene.  We inherit one copy of the CFTR gene from our mother, and one from our father.

    There are lots of different genetic variants which can occur in the CFTR gene.  Some of these are well recognised and described, and are so are called “common” or “recurrent” variants. It is also known that some variants tend to be more severe (i.e. they have a larger impact on the CFTR gene), and some are considered milder (i.e. they have a smaller impact on the CFTR gene).  Generally, more severe variants are associated with more severe disease, and vice versa.

    It is estimated that ~ 1 in 20 of us are carriers of CF (i.e. having a variant in only one copy of the CFTR gene).  Being a carrier of CF is not expected to have any implications for your health, but it may have reproductive implications.

  • What are “CFTR-related disorders”?

    CFTR-related disorders are other health conditions that are caused by disruption of the CFTR gene.  Generally, they are considered less severe than CF.

    CFTR-related disorders include chronic sinusitis, chronic cough or wheeze, pancreatitis and male infertility, due to congenital absence of the vas deferens (CAVD).

    CFTR-related disorders are typically caused by having a genetic variant in one copy of your CFTR gene, and a “milder” variant in the other copy and/or the poly 5T variant.  CFTR-related disorders can be very variable.  Two individuals with the same variants may be affected differently, or have no associated health problems at all.

  • What is the poly 5T variant?

    The ‘Poly5T variant’ describes a very common sequence in the CFTR gene.  In isolation, it is not typically associated with health problems.  However, if the ‘Poly5T variant’ occurs with another CFTR variant, on opposite copies of the CFTR gene (“in trans”), this can sometimes cause health problems (See CFTR-related disorders).

  • What do my results mean for me?

    The information below aims to support you in understanding your genetic test report.  However, please be aware that more personalised or specific information may be available on your report.

    If you have more than one genetic variant detected in your CFTR gene, the laboratory may request further testing of your family members (e.g. parents or siblings) to determine if those variants are on the same copy of the CFTR gene (“in cis”), or on opposite copies (“in trans”).  This information can be helpful in working out the significance of genetic results for your own health, and reproductive implications.

    CFTR result Possible implications
    A pathogenic1 variant in both copies of my CFTR gene (affected) ·         Typically associated with having CF or a CFTR-related disorder.

    ·         Increased risk of having a child with CF, depending on partner’s carrier status.
    A pathogenic variant in only one copy of my CFTR gene (a carrier) ·         Typically associated with being a carrier of CF.

    ·         Being a carrier of CF is not typically associated with any health problems.

    ·         Increased risk of having a child with CF, depending on partner’s carrier status.
    A pathogenic variant in one copy of my CFTR gene AND the poly 5T variant. ·         If the CFTR variant and the poly 5T variant are on the same copy of the CFTR gene, this is typically associated with being a “carrier” of CF.

    ·         If the CFTR variant and the poly 5T variant are on opposite copies of the CFTR gene, this is typically associated with being a carrier of CF +/- having a CFTR-related disorder.

    ·         Increased risk of having a child with CF, depending on partner’s carrier status.
    The poly 5T variant in one, or both, copies of my CFTR gene. ·         Having the poly 5T variant on both copies of the CFTR gene is associated with an increased risk of having a CFTR-related disorder.

    ·         Having the poly 5T variant on one copy your CFTR gene is not typically associated with health problems.

    ·         Both scenarios are associated with an increased risk of having a child with CFTR-related disorder, depending on partner’s carrier status.

    1A pathogenic variant is a variant that is believed to affect the function of the gene.

  • Does my partner need genetic testing?

    If you are planning to have children, you may want to know whether or not your partner is also a carrier of CF.  As above, it is estimated that 1 in 20 of us are carriers of a variant in one copy of the CFTR gene.

    If your partner is also a carrier of a variant in their CFTR gene, your chance of having a child with CF or a CFTR-related disorders is high. Couples at risk of having an affected child may be eligible for reproductive therapies (e.g. preimplantation genetic testing (PGT) or genetic testing during pregnancy). More information on prenatal care and testing.

    Your partner can request testing for the most common CFTR variants via their own GP, or another relevant health professional.  On the genetic test request, the doctor should state your details so that the laboratory can link the two results. This will help the laboratory to provide you with a more accurate report.  Requests for genetic testing which do not link to a relevant individual may be rejected.

    If your partner is also found to carry a CFTR variant, you may benefit from a referral to Clinical Genetics to discuss your results, and any reproductive options available to you.

    Please be aware that carrier testing for cystic fibrosis usually only checks for the 50 most common CFTR variants in the local population.  Consequently, while a normal test result is reassuring, it cannot totally rule out being a carrier of CF.  The laboratory take this into account when they provide adjusted risk figures on your genetic test report.  In general, if your partner does not have one of the 50 most common CFTR variants, the chance of having a child with CF, will be less than a couple in the general population.

  • Do my family members need genetic testing?

    It is likely that you inherited your variant(s) in CFTR from a parent.  This means that your siblings, and aunts and uncles, may also have one or more variants in their CFTR gene.  Your close relatives may wish to have genetic testing if they are planning to children, or if they have any symptoms consistent with CF, or a CFTR-related disorder.  As above, this can be arranged via their own GP (information for health professionals on how to request testing).  On the genetic test request, the doctor should state clearly your details, and their relationship to you, so that the laboratory can link the results.  Requests for genetic testing which do not link to a relevant individual may be rejected.

    If you have children, it is possible that your variant(s) in CFTR has been passed on to your children.  We do not recommend testing healthy children to check whether or not they are a carrier of a variant in their CFTR gene.  Testing can be undertaken when the child is old enough to make their own decision about whether or not to have testing. However, if your child has symptoms which could be consistent with CF or a CFTR-related disorder, they may warrant a referral to Paediatrics to explore this further, and to consider genetic testing.

    If you have more than one genetic variant detected in your CFTR gene, the laboratory may advise genetic testing of close relatives to help determine whether these CFTR genetic variants are on one copy of the CFTR gene (“in cis”), or if they are on opposite copies (“in trans”). This information can be helpful in working out the significance of genetic results for your own health, and reproductive implications.

  • Inheritance pattern of CF / risk of having a child with CF?

    CF and CFTR-related disorders are inherited in an autosomal recessive manner.  This means that couples where both parents are carrier for CF have a 1 in 4 (25%) chance of having a baby with the condition.  See below for other potential reproductive scenarios.

    Please be aware that more personalised or specific information may be available on your report.

    Partner 1 Partner 2 Typical reproductive outcomes
    Carrier of CF Carrier of CF ·         1 in 4 (25%) chance of having a child with CF.

    ·         2 in 3 (66%) of unaffected children will be a carrier of CF.
    Carrier of CF Not known to be a carrier ·         Very low.  Risk is not zero as no genetic test can entirely rule out being a carrier of CF.

    ·         1 in 2 (50%) chance that children will be a carrier of CF.
    Affected by CF Not known to be a carrier ·         Very low.  Risk is not zero as no genetic test can entirely rule out being a carrier of CF.

    ·         All unaffected children will be carriers of CF.
    Affected by CF Carrier of CF ·         1 in 2 (50%) chance of having a child with CF.

    ·         All unaffected children will be carriers of CF.

     

  • Reproductive options for couples at risk of having a child with CF.

    If your partner is also a carrier of a variant in their CFTR gene, your chance of having a child with CF or a CFTR-related disorders is high. Couples at risk of having an affected child may be eligible for reproductive therapies (e.g. preimplantation genetic testing (PGT) or genetic testing during pregnancy).

  • Do I need an appointment with Clinical Genetics?

    We do not see patients in the Genetics Clinic for carrier testing.  This can be requested via the GP, or another relevant health professional (see Requesting genetic testing).

    Couples at risk of having a child with CF or a CFTR-related disorder can be referred to Clinical Genetics discuss reproductive options.  More information on prenatal care and testing.

    We do not follow-up or treat patients with CF or CFTR-related disorders in the Genetics Clinic.  These patients are managed by relevant specialities (e.g. specialist CF clinics).

  • Screening for CF at birth and the sweat test.

    All babies in the UK undergo screening for CF at birth, via the day 5 blood spot (Guthrie test).  This measures immunoreactive trypsinogen (IRT).  Samples with abnormally raised IRT levels will undergo genetic testing to check for the most common variants in CFTR.

    Where genetic results, or clinical presentation, are unclear, a “sweat test” is sometimes undertaken. A sweat test measures the amount of salt in sweat, which will be abnormally high in someone with CF.

  • Further useful information.

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