TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: CFTRZ    
CFTR Gene, Full Gene Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Follow-up testing to identify mutations in individuals with a clinical diagnosis of cystic fibrosis (CF) and a negative targeted mutation analysis for the common mutations

 

Identification of mutations in individuals with atypical presentations of CF (eg, congenital bilateral absence of the vas deferens or pancreatitis)

 

Identification of mutations in individuals where detection rates by targeted mutation analysis are low or unknown for their ethnic background

 

Identification of patients who may respond to cystic fibrosis transmembrane conductance regulator (CFTR) potentiator therapy

 

This is not the preferred genetic test for carrier screening or initial diagnosis. For these situations, order CFP / Cystic Fibrosis Mutation Analysis, 106-Mutation Panel, Varies

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is not the preferred first-tier molecular test for carrier screening or diagnosis. It is used to identify mutations in individuals with a clinical diagnosis of cystic fibrosis (CF) when CFP / Cystic Fibrosis Mutation Analysis, 106-Mutation Panel, Varies is negative or uninformative.

 

This test includes next-generation sequencing to evaluate for mutations in the CFTR gene. Sanger sequencing may be performed to confirm detected variants.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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. Clinical diagnosis is generally made based on these features, combined with a positive sweat chloride test or positive nasal potential difference. CF can also have an atypical presentation and may manifest as congenital bilateral absence of the vas deferens (CBAVD), chronic idiopathic pancreatitis, bronchiectasis, or chronic rhinosinusitis. Several states have implemented newborn screening for CF, which identifies potentially affected individuals by measuring immunoreactive trypsinogen in a dried blood specimen collected on filter paper.

 

If a clinical diagnosis of CF has been made, molecular testing for common CF mutations is available. 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 the 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 isolated CBAVD.

 

The recommended approach for confirming a CF diagnosis or detecting carrier status begins with molecular tests for the common CF mutations (eg, CFP / Cystic Fibrosis Mutation Analysis, 106-Mutation Panel, Varies). This test, CFTR Gene, Full Gene Analysis, Varies may be ordered if 1 or both disease-causing mutations are not detected by the targeted mutation analysis. Full gene analysis, through sequencing and dosage analysis of the CFTR gene, is utilized to detect private mutations. Together, full gene analysis of the CFTR gene and deletion/duplication analysis identify over 98% of the sequence variants in the coding region and splice junctions.

 

Of note, FDA guidance has indicated that CFTR potentiator or combination chemical chaperone/potentiator therapies may improve clinical outcomes for patients with a clinical diagnosis of CF and at least 1 copy of a small subset of mutations. If one of the mutations associated with an FDA-approved therapy is identified, this information will be included in the interpretive report.

 

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

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A small percentage of individuals who have a diagnosis of cystic fibrosis (CF) may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic alterations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of CF. For carrier testing, it is important to first document the presence of a cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation in an affected family member.

 

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.

 

Technical limitations:

In some cases, DNA variants of undetermined significance may be identified.

 

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 addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

 

Evaluation tools:

Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.

 

Unless reported or predicted to cause disease, alterations in protein coding genes that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.

 

Reclassification of Variants-Policy:

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. At this time, it is not standard practice for the laboratory to systematically review likely pathogenic alterations or variants of uncertain significance that have been previously detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Rosenstein BJ, Zeitlin PL: Cystic fibrosis. Lancet 1998 Jan 24;351(9098):277-282

3. Strom CM, Huang D, Chen C, et al: Extensive sequencing of the cystic fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a comprehensive test. Genet Med 2003 Jan-Feb;5(1):9-14

4. De Boeck K, Munck A, Walker S, et al: Efficacy and safety of ivacaftor in patients with Cystic Fibrosis and the G551D gating mutation. J Cyst Fibros 2014 Dec;13(6):674-680 doi: 10.1016/j.jcf.2014.09.005

5. Currier RJ, Sciortino S, Liu R, et al: Genomic sequencing in cystic fibrosis newborn screening: what works best, two-tier predefined CFTR mutation panels or second-tier CFTR panel followed by third-tier sequencing? Genet Med 2017 Oct;19(10):1159-1163

Special Instructions Library of PDFs including pertinent information and forms related to the test