Cystic Fibrosis (CFTR) Sequencing

Background Information for Cystic Fibrosis (CFTR) Sequencing:
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.
Clinical Sensitivity: 97 percent.
Methodology: Bidirectional sequencing of the entire CFTR coding region, intron-exon boundaries, and two deep intronic mutations.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, large gene deletions/duplications and some deep intronic mutations will not be detected.