Cystic Fibrosis (CFTR) Sequencing with Reflex to Deletion/Duplication (Temporary Referral as of 12/07/20)

Background information for Cystic Fibrosis (CFTR) Sequencing with Reflex to Deletion/Duplication: 
Characteristics: Chronic sino-pulmonary disease, gastrointestinal malabsorption/pancreatic insufficiency, and obstructive azoospermia. Findings are often limited to a single organ system such as isolated pancreatitis, bilateral absence of the vas deferens, nasal polyposis, or bronchiectasis in non-classic cystic fibrosis (CF).
Incidence of Classic CF: 1 in 3,000 Caucasians or Ashkenazi Jewish, 1 in 8,000 Hispanics, 1 in 15,000 African Americans, 1 in 32,000 Asians.
Incidence of Nonclassic CF: Unknown.
Inheritance: Autosomal recessive.
Penetrance: High for severe mutations, variable for mild/moderate mutations.
Cause of Classic CF: Two deleterious CFTR mutations on opposite chromosomes.
Cause of Nonclassic CF:  Typically one severe and one mild/moderate CFTR mutations on opposite chromosomes.
Mutations Tested: Base pair substitutions and deletions/duplications within the coding region and intron-exon boundaries; additionally, two deep intronic mutations  (3849+10kbC>T and 1811+1.6kbA>G).
Clinical Sensitivity: 99 percent.
Methodology for Sequencing: Bidirectional sequencing of the entire CFTR coding region, intron-exon boundaries and two deep intronic mutations.
Methodology for Deletion/Duplication: Multiplex ligation-dependent probe amplification (MLPA) to detect large CFTR coding region deletions /duplications.
Analytical Sensitivity & Specificity for Sequencing: 99 percent.
Analytical Sensitivity & Specificity for MLPA: 98 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations.  Breakpoints for large deletions/duplications will not be determined. Regulatory region and some deep intronic mutations 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.