Interpretive Handbook

Cystic fibrosis (CF), in the classic form, is a severe autosomal recessive disorder characterized by a varied degree of chronic obstructive lung disease and pancreatic enzyme insufficiency. The incidence of CF varies markedly among different populations, as does the mutation detection rate for the mutation screening assay. To date, over 1,500 mutations have been described within the CF gene, named cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, deltaF508, accounts for approximately 67% of the mutations worldwide and approximately 70% to 75% in a North American Caucasian population. Most of the remaining mutations are rather rare, although some show a relatively higher prevalence in certain ethnic groups or in some atypical presentations of CF such as congenital bilateral absence of the vas deferens (CBAVD). Mutations detected by the assay performed in the Mayo Clinic Molecular Genetics Laboratory include the 23 mutations recommended by the American College of Medical Genetics as well as 83 other mutations.

Of note, CFTR potentiator therapies may improve clinical outcomes for patients with a clinical diagnosis of CF and at least 1 copy of the G551D mutation. 

These 106 mutations account for approximately 91% of CF chromosomes in a Northern European Caucasian population. Detection rates for several ethnic and racial groups are listed in the table below. Note that interpretation of test results and risk calculations are also dependent on clinical information and family history.

*Rates are for classical CF. Rates are lower for atypical forms of CF and for CBAVD.

CFTR mutations listed below are included in this panel.

See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions for additional information.

Confirmation of a clinical diagnosis of cystic fibrosis

Risk refinement via carrier screening for individuals in the general population

Prenatal diagnosis or familial mutation testing when the familial mutations are included in the 106-mutation panel listed above (if familial mutations are not included in the 106-mutation panel, order CFTRK/88880 CFTR Gene, Known Mutation)

Risk refinement via carrier screening for individuals with a family history when familial mutations are not available

Identification of patients who may respond to CFTR potentiator therapy

An interpretive report will be provided.

This assay will not detect all of the mutations that cause cystic fibrosis. Therefore, the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

In rare cases, DNA alterations of undetermined significance may be identified.

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

An interpretive report will be provided.

1. Quint A, Lerer I, Sagi M, Abeliovich D: Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening. Am J Med Genet A 2005;136(3):246-248

2. Bobadilla JL, Macek M, Fine FP, Farrell PM: Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat 2002;19(6):575-606

3. Sugarman EA, Rohlfs EM, Silverman LM, Alitto BA: CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med 2004;6(5):392-399

4. 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(5):387-391

5. Heim RA, Sugarman EA, Allitto BA: Improved detection of cystic fibrosis mutations in the heterozygous U.S. population using an expanded, pan-ethnic mutation panel. Genet Med 2001;3(3):168-176

6. Ramsey BW, Davies J, McElvaney NG, et al: A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation. NEJM 2011 Nov 3:365(18):1663-1672