Cystic Fibrosis (CFTR) 165 Pathogenic Variants with Reflex to Sequencing and Reflex to Deletion/Duplication

Background information for Cystic Fibrosis (CFTR), 165 Pathogenic Variants with Reflex to Sequencing and Reflex to Deletion/Duplication:
Characteristics of Classic Cystic Fibrosis (CF): Chronic sino-pulmonary disease, gastrointestinal malabsorption/pancreatic insufficiency, and obstructive azoospermia. Symptoms of a CFTR-related disorder are often limited to a single organ system such as isolated pancreatitis, bilateral absence of the vas deferens, nasal polyposis, or bronchiectasis.
Incidence: 1 in 2,300 Ashkenazi Jewish, 1 in 2,500 Caucasians, 1 in 13,500 Hispanics, 1 in 15,100 African Americans, 1 in 35,100 Asians.
Inheritance: Autosomal recessive.
Penetrance: High for severe pathogenic variants, variable for moderate and mild pathogenic variants.
Cause of Classic CF: Two severe, or one severe and one moderate, pathogenic CFTR variants on opposite chromosomes.
Cause of CFTR-Related Disorders: Two pathogenic CFTR variants on opposite chromosomes in any of the following combinations: two mild, one mild and one severe or one mild and one moderate.
Pathogenic Variants Tested: Refer to "Additional Technical Information" document.
Clinical Sensitivity for CF 165-Variants Test: Ashkenazi Jewish 96 percent; Caucasian 92 percent; Hispanic 80 percent; African American 78 percent; Asian American 55 percent.
Clinical Sensitivity for Sequencing and Deletion/Duplication Tests: 97 and 2 percent, respectively.
Methodology for 165-Variants Test: Polymerase chain reaction (PCR) and fluorescence monitoring.
Methodology for Sequencing: Bidirectional sequencing of the CFTR coding region and intron-exon boundaries.
Methodology for Deletion/Duplication: Multiplex ligation-dependent probe amplification (MLPA) to detect large CFTR coding region deletions/duplications.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplications will not be determined. Large CFTR inversions and regulatory region and intronic variants will not be detected.  

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.