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Cystic Fibrosis Screen
Test code(s) 10458X, 10463X (NY)


Question 1. What does a “heterozygous”, “homozygous”, or “compound heterozygous” result mean?

  • Heterozygousmeans the individual carries one copy of a mutation on one chromosome. If the mutation is associated with a recessive disease such as cystic fibrosis (CF), these individuals are called carriers. Carriers are typically unaffected, that is, they show no symptoms of the disease.
  • Homozygousmeans the individual carries two copies of the same mutation, one on each chromosome. If the mutation is associated with a recessive disease such as CF, these individuals are typically affected, that is, they show symptoms of the disease. However, the diagnosis is made clinically, based on clinical features and other lab studies.
  • Compound heterozygousmeans the individual carries one copy each of two different mutations, one on each chromosome. If the mutations are associated with a recessive disease such as CF, these individuals are typically affected. However, the diagnosis is made clinically, based on clinical features and other lab studies.

Diagnostic Criteria1

Phenotypic features of CF include, but are not limited to, the following:

  • Chronic sinopulmonary disease(chronic cough and sputum production, chronic wheeze and air trapping, obstructive lung disease on lung function tests, persistent colonization with pathogens commonly found in individuals with CF, chronic chest radiograph abnormalities, chronic pansinusitis, digital clubbing)
  • Gastrointestinal/nutritional abnormalities(meconium ileus, rectal prolapse, malabsorption/pancreatic insufficiency, steatorrhea, hypoproteinemia, fat-soluble vitamin deficiencies, failure to thrive, distal intestinal obstructive syndrome, recurrent pancreatitis, biliary sludging, elevation of transaminases and gamma-glutamyl transferase, direct hyperbilirubinemia, chronic hepatobiliary disease)
  • Obstructive azoospermia
  • Salt-loss syndromes(acute salt depletion, chronic metabolic alkalosis, hyponatremic hypochloremic dehydration)

The diagnosis of CF is established in individuals with the following:

  • One or more characteristic phenotypic features of CF, and
  • Evidence of an abnormality in cystic fibrosis transmembrane conductance regulator (CFTR) function based on one of the following:
    • Presence of two disease-causing mutations in the CFTR gene or
    • Two abnormal quantitative pilocarpine iontophoresis sweat chloride values (>60 mEq/L) or
    • Transepithelial nasal potential difference (NPD) measurements characteristic of CF

Question 2. What is the next step if my patient tests positive for one CF mutation?

It depends on the indication for the CF test:

  • For obstetrics and gynecology patients, guidelines recommend performing a CF screen on the male partner.2 If he is also a CF carrier, the fetus has a 25% risk of being affected with CF. Guidelines recommend offering the couple genetic counseling and prenatal testing if both partners are CF carriers.

    If her male partner’s result is negative, his residual risk to be a CF carrier is reduced, and the risk that the fetus is affected with CF is also reduced. The percent risk reduction is based on ethnicity, because the CF screen sensitivity varies by ethnic group.
  • For patients suspected of having CF, additional genetic testing may be considered to determine whether a second rare mutation, not detected by the standard CF screen, is present. Rare mutations in the CF gene may be detectable through two other assays. The Cystic Fibrosis Complete Rare Mutation Analysis, Entire Gene Sequence test (test code 10917X or 10919X [NY]) can detect point mutations in this gene. The Cystic Fibrosis Gene Deletion or Duplication test (test code 16080X or 16081X [NY]) can detect deletions or duplications of this gene. Please call 866-GENE-INFO to discuss the case and additional testing options.

Question 3. If my female patient carries a CF mutation, but her male partner carries a different CF mutation, is there still a risk that their offspring could be affected with CF?

Yes, the risk to offspring of this couple is 25%. CF is a recessive disease, so, when offspring inherit any two disease-causing CF mutations there is an increased risk to be affected with CF and CF-related conditions (like male infertility, for example). It does not matter if the two CF mutations are the same, or if they are different. This is due to the fact that if a child inherits a CF mutation from each parent, it means that he/she did not inherit a normal, working gene. However, since some CF mutations may be less severe and cause more mild symptoms, the exact symptoms of the child may be difficult to predict.

Question 4. How will submitting my patient’s ethnicity change the CF result / report?

Providing patient ethnicity does not change the CF result. A positive result is still positive, and a negative result is still negative, regardless of ethnicity provided. For negative results, the residual risk that your patient is still a CF carrier is provided in a table in the report, which is broken down by ethnicity. So, one can look up the residual carrier risk, by a patient’s specific ethnic group. The percent risk reduction is based on ethnicity, because the CF screen sensitivity varies by ethnic group.

Question 5. My patient has a family history of CF and has a negative CF screen result. Does this result guarantee that my patient is not a carrier of CF?

No, please call 866-GENE-INFO to discuss this case with a genetic counselor. Documentation of the specific CF mutations in the family will be necessary to determine the accuracy of the testing that was performed on your patient.

Question 6. My patient has a clinical diagnosis of CF, but the CF screen performed was negative. What should I do next?

For patients with a clinical diagnosis of CF, additional genetic testing may be considered to determine whether rare mutations, not detected by the standard CF screen, are present. Rare mutations can be detected using two other assays. The Cystic Fibrosis Complete Rare Mutation Analysis, Entire Gene Sequence test (test code 10917X or 10919X [NY]) can detect point mutations in this gene. The Cystic Fibrosis Gene Deletion or Duplication test (test code 16080X or 16081X [NY]) can detect deletions or duplications of this gene. Please call 866-GENE-INFO to discuss the case and additional testing options.

References

  1. CFTR-Related Disorders. GeneReviews. U.S. National Library of Medicine, National Institutes of Health website. http://www.ncbi.nlm.nih.gov/books/NBK1250/. Accessed September 11, 2012.
  2. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011;117:1028-1031.
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document: FAQS.10 Revision: 2