#ExistInterpData>Background information for Cystic Fibrosis (CFTR) 32 Mutations with Reflex to Sequencing and 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 in Panel: G85E (c.254G>A), R117H (c.350G>A), R334W (c.1000C>T), R347P (c.1040G>C), R347H (c.1040G>A), 394delTT (c.262_263delTT), A455E (c.1364C>A), I507del (c.1519_1521delATC), F508del (c.1521_1523delCTT), V520F (c.1558G>T), G542X (c.1624G>T), S549N (c.1646G>A), S549R (c.1645A>C or c.1647T>G), G551D (c.1652G>A), R553X (c.1657C>T), R560T (c.1679G>C), 621+1G>T (c.489+1G>T), 711+1G>T (c.579+1G>T), 1078delT (c.948delT), R1162X (c.3484C>T), W1282X (c.3846G>A), N1303K (c.3909C>G), 1717-1G>A (c.1585-1G>A), 1898+1G>A (c.1766+1G>A), 2183AA>G (c.2051_2052delAAinsG), 2184delA (c.2052delA), 2789+5G>A (c.2657+5G>A), 3120+1G>A (c.2988+1G>A), 3659delC (c.3528delC), 3849+10kbC>T (c.3717+12191C>T), 3876delA (c.3744delA), 3905insT (c.3773_3774insT). For specimens positive for R117H, the IVS-8/poly T (c.1210-12T[5_9] is analyzed by sequencing. The mutations tested are listed above according to the legacy nomenclature; the standard nomenclature is listed in parentheses. Panel mutations are reported according to the legacy nomenclature.
Clinical Sensitivity for reflex: 99 percent.
Methodology for Panel: PCR, oligonucleotide ligation assay (OLA), fluorescent hybridization probes, and capillary electrophoresis.
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: Rare diagnostic errors can occur due to primer and probe site mutations. The breakpoints of large deletions/duplications will not be determined. Regulatory region and intronic mutations will not be detected.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
See Compliance Statement C: www.aruplab.com/CS
||If only one pathogenic mutation is identified, then CFTR gene sequencing will be added. After CFTR gene sequencing, if less than two pathogenic mutations are identified, then CFTR deletion/duplication will be added. Additional charges apply.
||81220. If reflexed to Seq, add 81223. If reflexed to Del/Dup, add 81222