Text Size

Test Information

Cystic Fibrosis DNA Analysis

Test Code: 900616

Clinical Use

  • Detect cystic fibrosis carriers
  • Determine a couple’s risk of having a child with cystic fibrosis
  • Identify familial mutations in affected individuals
  • Diagnose cystic fibrosis (pre- and postnatally)


Clinical Background

Cystic Fibrosis (CF) is a common autosomal recessive disease affecting primarily Caucasians of Northern European descent, with an incidence of approximately 1 in 2,500 births and a carrier rate of 1 in 25. The disorder may be characterized by chronic obstructive pulmonary disease, pancreatic exocrine deficiency with malabsorption and malnutrition, and congenital bilateral absence of the vas deferens (CBAVD) leading to male infertility. Diagnosis of severe disease usually occurs within the first years of life and is based on chronic obstructive lung disease, persistent pulmonary infection (primarily Pseudomonas and Staphylococcus), meconium ileus, and pancreatic insufficiency with failure to thrive. Diagnosis is confirmed by a positive sweat chloride test and/or detection of a CF-associated mutation on both chromosomes. Treatment is focused on improved airway clearance, antibiotic therapy for infections, pancreatic enzyme replacement, proper nutrition, and psychological support; however, 90% of affected individuals die from lung damage. Median survival is approximately 30 years. Much milder forms of the disease are well described with clinical onset being delayed until adult life.

CF has been attributed to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of chromosome 7 (7q31.2). Over 1,000 mutations have been identified; however, the ?F508 mutation accounts for about 70% of all CFTR mutations in many, but not all, ethnic groups. Mutations result in a defective CFTR protein that, in turn, results in defective cellular chloride transport.

Individuals with CBAVD, chronic pancreatitis, or idiopathic pancreatitis have a significantly
increased risk of having 1 or more CF mutation(s).

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


  • Invader Mutation Analysis with Signal Amplification and Detection
  • Amplification of selected regions of the CFTR gene, followed by detection of wild-type and mutant sequences
  • Includes the 23 most common CF mutations as recommended by the American College of Medical Genetics.
  • Report form specifies mutations screened, mutations identified, and interpretive information
  • Synonyms: Cystic fibrosis transmembrane conductance regulator or CFTR, CF carrier screening

Interpretive Information

The following information will help with interpretation of test results. For additional assistance please contact Linda M. Pasztor, Ph.D., FACMG, at 602.685.5349, or 800.766.6721, ext. 5349.


Detection of 2 mutant alleles in conjunction with positive clinical findings or family history is consistent with CF. Failure to detect 1 or more mutant alleles in a symptomatic patient, however, does not exclude a diagnosis of CF. Approximately 18% of affected Caucasian individuals have only 1 detectable mutation, and 1% have no detectable mutations when using this screen. Sweat chloride testing should be performed in all suspected CF cases.

CF Chart

Carrier Detection

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

IVS8 5T/7T/9T Polymorphism

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

In summary, identification of an R117H mutation is followed by reflex testing for the 5T/7T/9T polymorphism in intron 8. If a 5T variant is identified, testing of family members is required to determine if the variant is in cis or trans. Genetic counseling is recommended.

I506V and I507V Variants

  • I506V and I507V are not associated with CF or CBAVD.
  • Individuals heterozygous for a ΔI507 or ΔF508 mutation who have an I506V or I507V variant on the other chromosome appear to be homozygotes on many CF detection assays (ie, carriers may be misclassified as CF-affected individuals). Thus, when results indicate a ΔI507 or ΔF508 homozygote, reflex testing for I506V and I507V is performed to rule out a false-positive CF test.

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. This risk is the same for each pregnancy, regardless of the outcomes of prior pregnancies.

Specimen Requirements

5 mL whole blood in a lavender-top (EDTA) tube or blue-top (citrate) tube (3 mL minimum). Complete the CF Information Profile (available from the laboratory) and include with the requisition. Specimen stability is crucial.

CPT Codes*

83891, 83892, 83896 x 23, 83900, 83901 x 17, 83908 x 23, 83912


  1. Cystic Fibrosis; CF. In Online Mendelian  Inheritance in Man, OMIMTM. John Hopkins University, Baltimore, MD. MIM number 219700. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/
  2. Genetic testing for cystic fibrosis. NIH Consensus Statement  1997;15(4):1-37
  3. Grody WW, Cutting GR, Klinger KW, et al: Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 2001;3:149-154.
  4. Kant JA, Mifflin TE, McGlennen R, et al: Molecular diagnosis of cystic fibrosis. Clin Lab Med 1995;15:877-898.
  5. Richards CS, Bradley LA, Amos J, et al. Standards and guidelines for CFTR mutation testing. Genet Med. 2002;4:379-391.
  6. Stern RC: The diagnosis of cystic fibrosis. N Engl J Med 1997;336:487-491.
  7. Tsui LC: The spectrum of cystic fibrosis mutations. Trends Genet 1992;8:392-398.
  8. Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med 2004;6:387-391.

* The CPT Codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the Payor being billed.