Cystic Fibrosis DNA Screen

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in the CFTR gene (cystic fibrosis transmembrane conductance regulator). This assay detects over 400 disease-causing variants in CFTR, and includes virtually all pathogenic or likely pathogenic variants present in the CFTR2 Database. (http://cftr2.org and Grody et al. 2001)

CFTR Intron 8 Poly(T) test is reported for individuals with the NM_000492.3:c.350G>A, p.R117H variant AND for evaluating CBAVD.

Indications for Testing Include

• Carrier testing in an individual with or without family history of CF, or in the spouse of a CF carrier
• Evaluate suspected CF
• Establish mutation status of CF-affected individual or obligate carrier
• Evaluate male infertility due to Congenital Bilateral Absence of Vas Deferens
• Follow up prenatal ultrasound findings that are suspicious for CF
• Evaluate idiopathic chronic pancreatitis

Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol 2017 Mar;129(3):e41-e55.

Deignan JL, et al. CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2020 Aug;22(8):1288-1295.

Grody WW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 2001, 3:149-54. 11280952

Ong T, Marshall SG, Karczeski BA, et al. Cystic Fibrosis and Congenital Absence of the Vas Deferens. 2001 Mar 26 [Updated 2017 Feb 2]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1250/

Test performed by targeted capture for CFTR followed by next-generation sequencing with Illumina technology. Sequences are aligned to the human genome reference (hg19). This assay sequences all exons and flanking intronic sequences of CFTR to detect single nucleotide variants, and small insertions and deletions. Large insertions and deletions are not detectable by this assay. Reporting is limited to pathogenic and likely pathogenic variants (i.e., variants of uncertain significance will not be reported). CFDNA May 2022-CFDNA reportable variants

This test was developed and its performance characteristics determined by the University of Washington Department of Laboratory Medicine and Pathology. It has not been cleared or approved by the US Food and Drug Administration. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. This test is used for clinical purposes. It should not be regarded as investigational or for research.

BLOOD:

• Adult: 5 mL LAVENDER TOP tube
• Child: 2 mL LAVENDER TOP tube
• Also acceptable: YELLOW TOP (ACD) tube
• Unacceptable: Heparin green top tubes

AMNIOCYTES or CULTURED CHORIONIC VILLUS CELLS:

• Two (2) T23 or One (1) T75 flask (minimum 1-T25 flask)

CHORIONIC VILLIS and/or TISSUE:

• In sterile tube or culture media, at least 5 mg tissue.

Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide, Lab Mnemonic Maternal Cell Contamination [MCC] for ordering and specimen requirements)

Blood: Refrigerate whole blood up to 1 week.

Amniocytes & cultured CVS cells: hold flasks at room temperature.

Chorionic villi &/or tissue: hold at room temperature

Saliva:
Contact laboratory for validated collection kit.

Outside Laboratories: Ship whole blood at ambient temperature for receipt within 1 week of specimen collection.- For cultured amniocytes or chorionic villus cells and for CVS or other tissue, transport and store at room temperature within 24 hours of obtaining CV or removing cultured cells from incubator.

Processing: Please notify genetics about amniocytes, cultured chorionic villus cells, chorionic villi or tissue.

Note: CF Mutation Analysis is to be done in-house UNLESS approved by Genetics to be sent to a referral lab. If this testing is for diagnosis of Congenital Bilateral Absence of the Vas Deferens (CBAVD), please note this in a comment when logging in the specimen. (The genetics lab will report additional information in these cases.).