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Cystic Fibrosis:  CFTR Gene Sequencing and deletion/duplication testing
Gene: CFTR;  chr7q31.2
Syndrome Information
Clinical Description:    Classic Cystic Fibrosis (CF) consists of progressive lung disease, exocrine pancreatic insufficiency, and male infertility.  Patients have elevated sweat chloride concentrations.  Patients sometimes termed 'non-classic' still meet diagnostic criteria for CF, but may have lower sweat chloride levels or may be pancreatic sufficient. 

CFTR-Related Disorder refers to patients older than 6 months with intermediate sweat chloride levels who may also have pancreatitis, chronic sinusitis, or infertility.  These patients are at risk for developing CF.

CFTR-Related Metabolic Syndrome is a diagnosis applied to asymptomatic infants with an inconclusive diagnostic work-us after newborn screening. Follow-up is necessary until the clinician can include or exclude the diagnosis. 

Inheritance Pattern:  Autosomal Recessive
Genotype-Phenotype Correlation:
There is a correlation between pancreatic status and CFTR mutation; however, lung disease seems to be more highly influenced by environmental factors or other modifier genes.
Test Information
Test Method:  Next Generation Sequencing (NGS) and/or Sanger sequencing of the coding regions and intron-exon boundaries of CFTR; Automatically reflexed to MLPA for deletion/duplication detection if sequencing is negative.

This test is also available as part of one or more NGS panels for cystic fibrosis and related disorders.

Clinical Utility: Identification of causative mutations in known or suspected cases of cystic fibrosis; targeted carrier testing of relatives of proband; predictive prenatal testing when familial mutations are known.   
Clinical Sensitivity: Sequencing:  Approximately 98% of classic CF is caused by point mutations in the CFTR gene. This sequence analysis will detect >99% of those point mutations. This analysis will not detect other types of mutations in the CFTR gene.

Del/Dup:  It is estimated that about 2% of CFTR mutations are large rearrangements, including deletions and duplications.  This test will detect full gene deletions and most previously reported multi- and single exon deletions and duplications, but not translocations or rearrangements limited to an intron.

Analytic Sensitivity:   

Sequencing:  >99% accuracy for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated;  Sequence analysis parameters are not designed to assess mosaicism. 

Del/Dup: Greater than 99% for MLPA probes analyzed.

Turn Around Time:   Sequencing:  Approximately 4 weeks 
Del/Dup:  up to 4 weeks
  Sample Requirement: 3-6ml whole blood in EDTA (purple topped) tubes.  (see Sample Requirements page or Pediatric or Adult blood sample algorithms for additional information)

For tests utilizing MLPA, we are only able to accept whole blood drawn in EDTA (purple or lavender top) tubes and Qiagen Puregene extracted DNA.

Fee and CPT Codes:    Sequencing:  $2450 for routine testing on a blood sample
CPT Code: 81223

MLPA:  $429 for routine testing on a blood sample
CPT Code:  81222

Please contact the lab to arrange testing for known mutations on blood or prenatal samples; Pricing and CPT codes will vary.  

Special Considerations
CFTR sequencing is most appropriate in the diagnostic setting when the patient has an atypical or non-classic presentation or when other mutation panels have failed to identify both causative mutations.  CFTR sequencing is not recommended in the carrier screening setting. 

CFTR deletion/duplication testing by MLPA analysis can be ordered separately. 

This test is also available as part of one or more NGS panels for cystic fibrosis and related disorders.

INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download.

Helpful Links
Sample Requirements
Requisition and Billing forms
Other NGS panels for cystic fibrosis and related disorders
Clinical information on Cystic Fibrosis
The Johns Hopkins CF Center
General Test Information page for a discussion of the uses and limitations of genetic testing
Patient and Family Page for general resources on genetic testing.