Cystic Fibrosis Screening


Detect Cystic Fibrosis (CF) carriers

Determine a couple’s risk of having a child with CF

Identify familial mutations in affected individuals

Diagnose CF post-natally

Clinical background


About Cystic Fibrosis (CF)

Cystic Fibrosis (CF) is one of the most common autosomal recessive diseases affecting Caucasians, with an incidence of approximately 1 in 3,000 births and a carrier rate of 1 in 25.1,2

It also occurs in other ethnic groups at a lower frequency. The disorder may be characterized by pulmonary disease, pancreatic insufficiency, liver disease and congenital bilateral absence of the vas deferens (CBAVD) leading to male infertility.1 Median predicted survival for CF patients is approximately 37 years,3 with lung damage causing the majority of deaths.2 A diagnosis of CF is confirmed by a positive sweat chloride test and/or detection of a CF-associated mutation on both chromosomes.1

ACMG Disclaimer:  These standards and guidelines are designed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services.  Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results.  In determining the propriety of any specific procedure or test, the clinical molecular geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the laboratory record the rationale for any significant deviation from these standards and guidelines.

Cause And Recommended Screening

CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of chromosome 7 (7q31.2).1 Mutations result in a defective CFTR protein that, in turn, results in defective cellular chloride transport. Over 1,900 mutations, most of which occur at frequencies of <0.01%, have been identified.4 One mutation, delf508, accounts for approximately 70% of all CFTR mutations in many, but not all ethnic groups.1,4 In 2011, almost 86% of patients in the Cystic Fibrosis Foundation patient registry were reported to have at least one copy of delf508, and 47% had two copies.3


The American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recommend screening for 23-45 common CFTR mutations that were chosen primarily based on their frequency in Ashkenazi Jewish and non-Hispanic Caucasian populations. CF is more common in these ethnic groups, and the initial 23 mutations account for 94% of mutant alleles in Ashkenazi Jews and 88% in non-Hispanic Caucasians.1,2 Although the 23 mutations account for a lower percentage of mutant alleles in other ethnicities, ACMG and ACOG consider the panel of mutations pan-ethnic and recommend offering screening to all patients.1,2 PreCF includes the 23 ACMG/ACOG-recommended mutations and all of the 22 other multi-ethnic mutations as recommended by the ACMG for expanded use in the USA population. One other mutation has been added to help diagnose CABVD for a total of 46 mutations. These mutations are selected based on their frequency in the population as well as their association with the classic CF phenotype. Other mutations were not selected because their frequency is less than 0.01% and many of them are associated with milder CF phenotypes making the interpretation of the results difficult.


Individuals Suitable For Testing

  • Individuals with a family history of CF or CFTR mutations
  • Symptomatic children and adults
  • Males with CBAVD
  • Patients with chronic or idiopathic pancreatitis
  • Reproductively active individuals or couples


  • Agena Biosciences MassArray® Platform
  • Amplification of selected regions of the CFTR gene, followed by detection of wild-type and mutant sequences
  • Report form specifies mutations screened, mutations identified, and interpretive information

Interpretive Results

PreCF testing Includes the 45 most common CF mutations as recommended by ACMG and ACOG; this includes the all of the recommended mutations with a frequency greater than 0.01% in the US Caucasian population. These mutations reflect relevance to classical CF phenotypes. One of these mutations (R117H) is only relevant if it is found in combination with a 5T or 7T on Intron 8, so that mutation is also measured for either form. The 2014 recommendations from the ACMG include the mutations that are ‘pertinent to classical CF risk rather than the milder phenotypes’. There are some mutations that may be associated with mild or severe CF depending on the mutations with which they are paired, thereby complicating the interpretation of the severity of the risk for CF. As there are over 1900 mutations possible in the CFTR gene, interpretation of the CF risk becomes increasingly complicated as the testing panel expands to include milder mutations.

















Informed Consent

Patients tested should know that PreCF is testing for the most common mutations associated with cystic fibrosis. There are many other less common mutations representing at least 5% of the risk for cystic fibrosis. PreCF does not test for all mutations but it does measure the most complete listing of CF mutations recommended by the ACMG and ACOG. A goal of informed consent for CF carrier testing is to make couples aware that there is a range of clinical outcomes that cannot be predicted to 100% accuracy.



Genetic Counseling:

The following information will help with interpretation of test results.

Additional assistance is available from our Genetic Counselors

by contacting


Detection of 2 mutant alleles in conjunction with positive clinical findings or family history is consistent with CF. Failure to detect 2 mutant alleles in a symptomatic patient, however, does not exclude a diagnosis of CF. Not all individuals with CF will have 2 mutations identified by this test. Sweat chloride testing should be performed in all suspected CF cases.


Carrier Detection

The presence of a single CF mutation in an asymptomatic individual identifies that person as a carrier. As shown in Table 2 below, absence of a CF mutation significantly reduces, but does not eliminate, the risk of being a carrier. The residual risk of being a carrier (i.e., of having a CF mutation not screened for in this assay) is influenced by the individual’s ethnicity and clinical and family history. If clinically indicated, additional testing is available.

  1. Detection rates and residual risk estimates are based on the 23 ACMG/ACOG-recommended mutations.6 Exact figures are unavailable for this panel, but because the panel tests more mutations, detection rates may be slightly higher and risk rates after a negative CF screen may be slightly lower than the figures in this table.
  2. Risks are based on the assumption that there is no family history of CF.



IVS8 5T/7T/9T Variant

  • A single 5T variant with an R117H mutation on the same chromosome (in cis) acts as a classic CF mutation. Thus, an individual with this genotype is a CF carrier.1 A 5T variant occurring in trans (on the opposite chromosome) with an R117H mutation may result in CBAVD.1
  • A 7T or 9T variant in cis with an R117H mutation acts as a mild CF mutation.1 Thus, an individual with this genotype is a CF carrier. When coupled with a classic CF mutation, male patients may have CBAVD.

Identification of an R117H mutation and either a 5T or 7T in conjunction with the R117H variant will be reflexed for sequencing to determine the cis or trans positioning as described above. Testing of family members may be required to determine if the variant is in cis or trans.1 Genetic counseling is recommended.


Risk Calculation for a CF-affected Fetus

A couple’s risk of having a CF-affected fetus = [(mother’s carrier risk) (father’s carrier risk)] ÷ 4.1 This risk is the same for each pregnancy, regardless of the outcomes of prior pregnancies.



  1. American College of Medical Genetics. Technical standards and guidelines for CFTR mutation testing. 2006 ed. Updated April 26, 2006. Accessed November 21, 2013.
  2. Committee on Genetics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 486, April 2011. Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011;117:1028-1031.
  3. Cystic Fibrosis Foundation Patient Registry. 2011 Annual Data Report. Improvement/PatientRegistryReport/. Accessed November 22, 2013.
  4. Cystic Fibrosis Mutation Database. Toronto, Ontario, Canada: Cystic Fibrosis Centre at the Hospital for Sick Children. Updated April 25, 2011. Accessed November 22, 2013.
  5. Sosnay PR, Siklosi KR, Van Goor F, et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013;45:1160-1167.
  6. Committee on Genetics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 325, December 2005. Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2005;106:1465-1468.
  7. Watson et al: Cystic Fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genetics in Medicine Sept 2004; Vol 6, No 5.


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