Patient Test Information

CF Mutation Panel

Also known as:

Cystic Fibrosis Genotyping; CF DNA Analysis; CF Gene Mutation Panel; CF Molecular Genetic Testing

Formal name:

Cystic Fibrosis Gene Mutation Panel

Related tests:

Sweat Test; Trypsinogen; Chymotrypsin

Why Get Tested?

To detect cystic fibrosis (CF) gene mutations, to establish CF carrier status, and to to evaluate the risk of having a baby with CF; to establish the diagnosis of CF in an individual

When to Get Tested?

As part of routine care when a woman is pregnant or considering pregnancy for the first time; when someone wants to know their carrier status; when screening newborns for CF in some states; when someone has signs and symptoms of CF

Sample Required?

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 prenatal (amniocentesis or chorionic villus) specimens

Test Preparation Needed?

None

How is it used?

Cystic fibrosis (CF) gene mutation testing can be done to screen the general population or to screen a targeted (higher risk) subset of the population for carrier status. It can be used to confirm the diagnosis of cystic fibrosis in a symptomatic person with an elevated immunoreactive trypsinogen (IRT) or positive sweat chloride test.

Cystic fibrosis 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 mutation panel can be used as part of a prenatal workup to establish carrier status in prospective parents and therefore determine the risk of CF in their infant. 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. The American College of Medical Genetics recommends that a positive result for the mother should include the recommendation of testing her partner and at-risk family members and that all positive results for diagnostic tests or for positive/positive couple screening should indicate the need for genetic counseling. In addition, all CFTR carriers and any individuals who have a family history of CF should also be referred for genetic counseling.

CF gene mutation testing can also be used for prenatal diagnosis if both parents are known to be carriers and if their gene mutations have been previously identified. DNA from amniocentesis and chorionic villus sampling procedures, although somewhat invasive, can be used to test the fetus for the known parental mutations.

When is it ordered?

A CF gene mutation panel may be ordered:

  • For prospective parents prior to conception or for a fetus to diagnose CF when mutations have been identified in both parents
  • To determine carrier status whenever it is desired or recommended and/or when someone has a close relative who has been diagnosed with CF
  • When a newborn infant has meconium ileus or when a person has symptoms of CF such as salty sweat, persistent respiratory infections, wheezing, persistent diarrhea, foul-smelling bulky greasy stools, malnutrition, vitamin deficiency, or male infertility
  • To confirm a CF diagnosis following a positive sweat chloride or IRT test

What does the test result mean?

Diagnostic test results
If a CF gene mutation panel is positive - it comes back with two identified gene mutations - then the person has CF. 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 mutation or is negative and the patient is symptomatic, further mutation testing, a sweat chloride test, and/or other laboratory testing to check 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.

Carrier test results
If the CF gene mutation panel comes back with a single identified mutation and the patient is asymptomatic, then chances are that the person is a CF carrier. This may be information some individuals want to know before having children. If someone is identified as a carrier, then the siblings of this person may also want to verify their carrier status.

If the panel comes back negative for mutations and the person is asymptomatic, chances are 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 detection of CF 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.

Doctors may have varying approaches to screening and diagnosing CF, and gene mutation testing may involve a series of steps. Sometimes, a doctor 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 doctor 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 doctors 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.

What is being tested?

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 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome seven to identify carriers of the disease and to screen for or help make a diagnosis of CF.

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. They are not ill, but they can pass their abnormal CF gene copy on to their children.

To date, more than 1,500 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 pick up 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 seven 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 the disease.

How is the sample collected for testing?

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, or prenatal (amniocentesis or chorionic villus) specimens may also be used.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

  1. Will this CF gene mutation panel pick up 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).

  2. Does my risk of being a carrier vary depending on my ancestry?

    Generally, the frequency of CF carriers is highest in Caucasians (1/25), about half that in people with Hispanic Caucasian or African ancestry, and about half that again in people of Asian ancestry. Some ethnic groups, such as individuals of Eastern European Jewish descent, may show CF confined to a very limited number of mutations. 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.

  3. What are the advantages of the DNA-based blood test over other CF screening tests?

    Generally, the DNA-based mutation test is much more specific than other screening tests, which may yield abnormal results for non-CF reasons. Also, these other screening tests may be restricted as to when they can be applied (for example, newborns cannot be tested with sweat chloride until about two months of age). Furthermore, DNA-based testing is the only reliable means of identifying carriers of CF mutations, and it is in this capacity that the testing is being most widely applied.

  4. Do states require or offer newborn screening for CF? Do I need to request it?

    Every state's newborn screening program includes a test for CF so you will not need to request it. The method used may vary, with some states performing only a test to determine the blood level of a chemical called immunoreactive trypsinogen (IRT) and others performing both an IRT and the DNA-based mutation test when the IRT level is high.