Also known as: cystic fibrosis genotyping, cystic fibrosis gene mutation testing
Name: Cystic fibrosis gene mutation panel
Related tests: Trypsin and chymotrypsin
Why get tested?
To find cystic fibrosis (CF) gene mutations, to show whether someone is a CF carrier or to confirm a diagnosis of CF in an individual. The American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recommend targeted gene testing when a couple is planning a pregnancy or in early pregnancy
When to get tested?
When a newborn baby has meconium ileus or when a person has symptoms of CF (salty sweat, recurrent respiratory infections, shortness of breath, persistent diarrhoea, mucous and foul-smelling stools, malnutrition, vitamin deficiency, male infertility); if a person has a positive sweat test or IRT test, or has close relatives diagnosed with CF; when a patient is seen by an obstetrician for pre-conception counselling or a prenatal visit, or is about to have genetic counselling before prenatal screening and wants to know their CF carrier status; when prenatal diagnosis is being considered because both parents are known to be CF carriers.
Sample required?
A blood sample from a newborn baby’s heel, a blood spot on filter paper or a blood sample from a vein. A cheek swab or prenatal samples (amniocentesis or chorionic villi) can also be used.
What is being tested?
The CF gene mutation test identifies mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7. Every cell in the human body (except sperm and eggs) has 46 chromosomes (23 inherited from the mother and 23 from the father). The genes on these chromosomes contain the information for making proteins that control the body’s functions. Cystic fibrosis is caused by a mutation in each of the two copies of the CFTR gene located on chromosome 7: for cystic fibrosis to occur, both copies (alleles) of this gene must be mutated. If only one copy of the gene pair is mutated, the person is a CF carrier. Carriers are not ill; they generally have no symptoms of CF, but they can pass their mutated copy of the CF gene on to their children.
More than 1,000 different mutations of the CFTR gene have now been identified, but only a few of them are common. Most cases of cystic fibrosis in the United States are caused by a mutation called delta F508 (F508). The recommendations of the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) call for a standard panel for CF gene mutation testing. Some laboratories use extended panels that can test for up to 97 mutations, picking up rare mutations typical of specific ethnic groups. Most rare mutations are private, i.e. unique to a single person or family.
With the CF gene mutation test, the laboratory specifically examines 23 mutations of the CFTR gene on each chromosome 7. If the initial panel of 23 mutations reveals one, further tests for other, less common mutations may be indicated if the person is suspected of having CF.
How is the sample collected for testing?
A blood sample is taken from a newborn baby’s heel, as a blood spot on filter paper, or from a vein. Cheek swabs or prenatal samples (amniocentesis or chorionic villi) can also be used.
How is it used?
When is it requested?
How is the result interpreted?
Is there anything else I should know?
How is it used?
The CF gene mutation test can be used to screen the general population or a target (high-risk) group for carrier status.
It can be used to confirm a diagnosis of CF in a patient with symptoms who has a raised immunoreactive trypsinogen (IRT) or a positive sweat test. The test can be used to establish the carrier status of prospective parents and so determine the risk of CF in their children. Usually the mother is tested first; if she is not a carrier, her children can only be carriers through the father, so, following this logic, the father is not tested. If, on the other hand, the mother is a carrier, the father is tested too. With couple testing, both parents are tested at the same time. In either case, follow-up genetic counselling is needed to give the couple information on what being a carrier means and to explain the limitations of the test, including the residual risk of being a carrier even if the test is negative.
The test can be used for prenatal diagnosis if the parents are known to be carriers and their mutations have previously been identified. DNA obtained from amniocentesis or chorionic villi, although these procedures are invasive, can be used to test the foetus for the parents’ mutations.
When is it requested?
A doctor may request the test to rule out CF when a patient has symptoms such as salty sweat, persistent respiratory infections, shortness of breath, persistent diarrhoea, mucous and foul-smelling stools, malnutrition, vitamin deficiency or male infertility.
The test may be requested to confirm a diagnosis of CF after a positive sweat test or a positive IRT.
How is the result interpreted?
If the test is positive (two mutations have been identified), the patient has CF.
However, the test cannot predict how severe or mild the symptoms will be. Patients with the same type of mutation can have very different manifestations.
If the test reveals a single mutation or is negative and the patient has symptoms, a sweat test and/or other laboratory tests to check organ function are justified in addition to the mutation test. The patient may have a rarer form of CF that has not been identified, or may have a lung or pancreatic disease or other condition other than CF.
If the test identifies a single mutation and the patient has no symptoms, the person is probably a CF carrier. This can be useful information for people who want to know their status before having children.
If you have been identified as a carrier, your brothers and sisters can also check their carrier status. If the test is negative for mutations and the patient has no symptoms, the patient probably does not have CF and is not a carrier. There is still a small risk that some people may carry a rare mutation not identified by the standard panel.
Is there anything else I should know?
Early detection of CF allows patients to be referred to CF centres for specialist care, individual treatment plans and careful monitoring. Starting treatment with oral enzyme supplements and fat-soluble vitamins, teaching how to clear mucus from the airways and teaching how to recognise respiratory infections can improve the patient’s quality of life and minimise complications.
1. Can the CF mutation test identify other genetic diseases?
2. What is my risk of being a carrier if I am of mixed ethnicity?
3. What are the advantages of a DNA-based blood test over other CF screening tests?
4. Does the state require or offer newborn screening for CF? Do I need to ask for it?
1. Can the CF mutation test identify other genetic diseases?
No, it is specific to CF. All other genetic diseases require specific DNA tests (assuming that the gene and the mutations causing them are known).
2. What is my risk of being a carrier if I am of mixed ethnicity?
In general, the carrier frequency is highest in white people (1 in 25), about half that in white Hispanics and African Americans, and about half again in Asians. Some ethnic groups, such as people of Eastern European Jewish descent, may have CF limited to a very small number of mutations, and a test with a limited mutation panel may be preferred. Given the continuing growth of ethnic mixing in the US, historical data and statistical risks are changing.
3. What are the advantages of a DNA-based blood test over other CF screening tests?
In general, a DNA mutation test is more specific than other screening tests, which can give abnormal results for reasons unrelated to CF. These other screening tests may also have limitations (for example, newborn babies cannot have a sweat test until they are two months old). In addition, DNA-based tests are the only reliable way to identify mutation carriers, and it is precisely because of this ability that the test is becoming more and more widely used.
4. Does the state require or offer newborn screening for CF? Do I need to ask for it?
Most US states offer the CF test as a newborn screening test, but requirements differ from state to state, as defined by each state’s public health department. All states now have their own mandatory newborn screening programmes, but in some of them CF screening is not mandatory, so you may need to ask for it.