To detect cystic fibrosis (CF) gene mutations; to screen for or help diagnose CF; to determine whether you are a carrier of a CF genetic mutation and to evaluate the risk of having a baby with CF
Cystic Fibrosis (CF) Gene Mutations Testing
When screening newborns for CF (all U.S. states screen for CF and some states use this test for screening); when an older child or adult has signs and symptoms of CF or a positive CF screening test; when someone wants to know their carrier status, such as a woman who is pregnant or considering pregnancy for the first time
A blood sample drawn from an infant's heel by collecting a spot of blood onto filter paper; for older children or adults, a blood sample obtained by inserting a needle into a vein in the arm; sometimes a scraping of the inner cheek (buccal swab) or, for prenatal testing, amniotic fluid obtained through amniocentesis or a chorionic villus sample
Cystic fibrosis (CF) is an inherited disease that affects mainly the lungs, pancreas, and sweat glands. It leads to the production of thick, sticky mucus and can cause recurrent respiratory infections and impaired function of the pancreas. The CF gene mutation panel detects the common mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7 to screen for or diagnose CF or to identify carriers of the disease.
Each cell in the human body (except sperm and eggs) has 46 chromosomes (23 inherited from the mother and 23 from the father). Genes on these chromosomes form the body's blueprint for producing proteins that control body functions.
Cystic fibrosis is caused by a mutation in each of the two copies of the CFTR gene (one copy from each parent). Both copies (alleles) of this gene pair must be abnormal to cause CF. If only one copy is mutated, the individual is a CF carrier. Carriers do not generally have any CF symptoms, but they can pass their abnormal CF gene copy on to their children.
To date, more than 2,000 different mutations of the CFTR gene have been identified, but only a few of the mutations are common. The majority of cystic fibrosis cases in the U.S. are caused by a mutation called deltaF508 (F508).
Recommendations by the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) have led to the adoption of a standard CF gene mutation panel. It includes 23 of the most common mutations (those with frequencies greater than 0.1% in the general U.S. population).
Some laboratories use expanded panels of up to 100 or more mutations designed to detect rare mutations particular to specific ethnic populations. These may provide slightly better sensitivity to detect mutations in some ethnic populations but are not recommended by ACOG for general screening. Some rare mutations are seen in only a few individuals and may not be detected with routine testing, even with an expanded panel.
In a CF gene mutation panel, the laboratory specifically examines the CFTR gene on each chromosome 7 for the 23 mutations. If the initial panel of mutations demonstrates a single mutation, additional testing for other less common mutations may be indicated if the individual is suspected of having CF.
A blood sample is drawn from an infant's heel by collecting a spot of blood onto filter paper; for older children and adults, a blood sample is obtained by inserting a needle into a vein in the arm. A scraping of the inner cheek, called a buccal swab sample, may be collected. For prenatal testing, a sample of amniotic fluid may be collected using amniocentesis or a chorionic villus sample may be collected.
No test preparation is needed.
- How is it used?
Cystic fibrosis (CF) gene mutation testing may be used to screen for CF in newborns in some states (all U.S. states screen for CF and some states use this test for screening), to help diagnose CF, or to determine whether an individual is a carrier of a CF genetic mutation.
CF gene mutation testing may be used to follow up a positive initial test, such as an elevated immunoreactive trypsinogen (IRT) or positive sweat chloride test, to confirm the diagnosis of cystic fibrosis.
The CF mutation panel can be used as part of prenatal testing to determine whether prospective parents are carriers of a CF gene mutation and therefore at risk of passing the gene mutation to future children.
The American College of Obstetricians and Gynecologists recommends that carrier screening be made available to all women of reproductive age to identify couples at risk of having a child with CF. This is typically done by sequential testing:
- In a sequential strategy, the mother is usually tested first. If she is not a carrier, then any child she had would, at most, be a carrier from the father's side. Using this logic, the father is not tested.
- A positive result for the mother should include the recommendation of testing her partner and at-risk family members.
All individuals with positive results for diagnostic tests or partners who are both identified as carriers should receive genetic counseling. In addition, any individuals who have a family history of CF should be referred for genetic counseling.
CF gene mutation testing can also be used for prenatal diagnosis if both parents are known to be carriers. DNA from amniocentesis and chorionic villus sampling procedures, although somewhat invasive, can be used to test the fetus for the mutations that have been identified in the parents.
- When is it ordered?
A CF gene mutation panel may be ordered:
- When you or your partner are planning to become pregnant
- During the first trimester of pregnancy or the first prenatal visit
- When someone has a close relative who has been diagnosed with cystic fibrosis
- For an infant, soon after birth
- When a person has had a positive CF screening test such as a sweat chloride conductivity test or IRT test
When a person has signs and symptoms of CF, such as:
- Very salty sweat
- Frequent respiratory infections, such as bronchitis or pneumonia
- Wheezing, shortness of breath
- Persistent diarrhea and/or foul-smelling, bulky, greasy stools
- Delayed growth or poor weight gain (failure to thrive)
- Vitamin deficiency, malnutrition
- Infertility in men
- What does the test result mean?
CF gene mutation testing results must be interpreted in the context of the person's signs and symptoms and physical examination as well as medical and family history, ethnic background, and results of other laboratory tests.
If a CF gene mutation panel identifies two copies of gene mutations, then the person is diagnosed with cystic fibrosis. The test, however, cannot predict how severe or mild the symptoms may be. People with the exact same mutations may have very different outcomes.
If the CF gene mutation panel reveals a single copy of a mutation or is negative and the person tested has signs and symptoms of CF, then further mutation testing, a sweat chloride test, and/or other laboratory testing to evaluate organ function are warranted. The person may have a more rare form of CF that has not been identified or may have a lung or pancreatic disease or condition other than cystic fibrosis. The person may also be a carrier since some CF carriers may experience signs and symptoms related to CF.
If the CF gene mutation panel is positive for a single copy of a mutation and the person tested does not have signs and symptoms, then it is likely that the person is a CF carrier. If someone is identified as a carrier, then the siblings of this person may also want to verify their carrier status.
If the panel results are negative for mutations and the person has no signs or symptoms, then it is likely that the person does not have CF and is not a carrier. There is still a slight risk that someone who tests negative could be a carrier of a rare mutation not identified with the standard panel.
- Is there anything else I should know?
Early diagnosis of cystic fibrosis allows those affected to be referred to CF centers for specialized care, individualized treatment plans, and careful monitoring. Beginning treatments such as taking oral enzyme supplements and fat-soluble vitamins, learning how to clear mucus out of airways, and learning to recognize respiratory infections can improve a person's quality of life and minimize CF complications.
Healthcare practitioners may have varying approaches to screening and diagnosing CF, and gene mutation testing may involve a series of steps. Sometimes, a healthcare practitioner will choose to order a standard panel that includes 23 of the most common mutations. If results are negative and the clinical suspicion is still high that a person has CF, the healthcare practitioner may then request that an expanded panel be performed, or a negative result may automatically generate (reflex) a request for an expanded panel.
Based on the ancestry of the individual tested, some healthcare practitioners may immediately start with the expanded panel. In either scenario, a negative screening panel result may lead to a request for gene sequencing, a method that can identify rare mutations not detected by the standard or expanded panel.
- Will this CF gene mutation panel detect any other genetic diseases?
No, it is only checking for specific CF mutations. Currently, every genetic disease requires specific DNA testing to identify it (assuming that the gene and mutations causing it are known).
- Does this test detect all genetic causes of cystic fibrosis?
No. To date, more than 2,000 different mutations of the CFTR gene that cause cystic fibrosis have been identified, but only a few of the mutations are common. Some laboratories use the standard panel recommended by the American College of Medical Genetics and the American College of Obstetricians and Gynecologists that tests for 23 of the most common mutations (those with frequencies greater than 0.1% in the general U.S. population). Some laboratories offer expanded panels of up to 100 or more mutations. However, even these will not detect all genetic causes of cystic fibrosis.
- Does my risk of being a carrier vary depending on my ethnic background?
Yes. Generally, the frequency of CF carriers is highest in Caucasians and Ashkenazi Jewish populations and is lower in other ethnic groups. According to the American College of Obstetricians and Gynecologists, the risk of being a carrier before genetic testing for different ethnic groups are estimated as follows:
- Caucasians: 1 in 25
- Ashkenazi Jewish: 1 in 24
- Hispanic white: 1 in 58
- African American: 1 in 61
- Asian American: 1 in 94
Since the ancestry of the U.S. population is becoming increasingly blended, the historical data and statistical risks are changing. Quoted risks based on ancestry are estimates, and the risk for individuals of mixed ancestry may be unknown. Some families may also carry the additional risk of specific rare mutations within their family tree.
- Do all states require or offer newborn screening for CF? Do I need to request it?
Every state's newborn screening program includes a test for cystic fibrosis, so you will not need to request it. The method used may vary, with some states performing a blood test to determine the level of immunoreactive trypsinogen (IRT) and others screening for CF with gene mutation testing.