Test ID: CFTRK
CFTR Gene, Known Mutation

Diagnostic confirmation of cystic fibrosis when familial mutations have been previously identified

Carrier screening of at-risk individuals when a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified in an affected family member

Identification of patients who may respond to CFTR potentiator therapy

Documentation of the specific familial mutation(s) must be provided with the specimen in order to perform this test.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

• Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet
• Informed Consent for Genetic Testing

Polymerase chain reaction (PCR)/DNA sequencing and/or dosage analysis (multiplex ligation-dependent probe amplification: MLPA) is utilized to test for the presence of a specific mutation previously identified in an affected family member.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Forms:

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

2. Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet (Supply T521) in Special Instructions

3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) with the specimen.

Additional Information: Patient education brochures in English (Supply T548) and Spanish (Supply T563) are available upon request.

Specimen must arrive within 96 hours of collection.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:        

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MCC/88636 Maternal Cell Contamination, Molecular Analysis on the maternal specimen.

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.

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, CFPB/9497 Cystic Fibrosis Mutation Analysis, 106-Mutation Panel). This test, CFTR Gene, Full Gene Analysis may be ordered if 1 or both disease-causing mutations are not detected by the targeted mutation analysis (CFPB/9497 Cystic Fibrosis Mutation Analysis, 106-Mutation Panel). Full gene analysis, 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, CFTR potentiator therapies may improve clinical outcomes for patients with a clinical diagnosis of CF and at least 1 copy of the G551D mutation. 

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

An interpretive report will be provided.

An interpretive report will be provided.

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order CFPB/9497 Cystic Fibrosis Mutation Analysis, 106-Mutation Panel or CFTRM/88876 CFTR Gene, Full Gene Analysis.

Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with cystic fibrosis.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to an erroneous interpretation of results.

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.

Rare polymorphisms exist that could lead to false-negative or false-positive results. If the 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.

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

2. 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

3. 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

DNA sequencing and/or dosage analysis by multiplex ligation-dependent probe amplification (MLPA) is used to test for the presence of a specific mutation previously identified in an affected family member. (Unpublished Mayo method)

Wednesday; 10 a.m.

CFTR Gene, Known Mutation

81221-CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; known familial variants

81265 - Comparative analysis using Short Tandem Repeat {STRI markers; patient and comparative specimen (eg. Pretransplant recipient and donor germline testing, posttransplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample! and donor testing. twin zygosity testing, or maternal cell contamination of fetal cells) (if appropriate)

Amniotic Fluid Culture for Genetic Testing

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

Fibroblast Culture for Genetic Testing

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)