Cystic fibrosis: Carrier screening
- Katharine D Wenstrom, MD
Katharine D Wenstrom, MD
- Professor of Obstetrics and Gynecology
- Alpert School of Medicine at Brown University
Cystic fibrosis (CF) is a life-limiting autosomal recessive disease affecting the airways, pancreas, liver, intestines, sweat glands, and, in males, the vas deferens. It is the most common monogenic disorder in non-Hispanic whites of Northern European descent, with a carrier frequency of 1/24 to 1/25 and birth prevalence of 1 in 2500. Carrier screening is offered to couples planning pregnancy or in early pregnancy to identify those at risk of conceiving a child with classic CF.
This topic will review CF carrier screening and reproductive options for carrier couples, including prenatal diagnosis. Other issues related to CF are discussed separately, including:
CF is caused by mutations in a single large gene on chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which regulates chloride channel function of epithelial cells of the sweat gland, airway, pancreas, and intestine. Clinical disease occurs when disease-causing mutations are present in both copies of the CFTR gene. Over 1900 different mutations in the CF gene have been identified, although the vast majority of CFTR mutations occur at frequencies less than 1/1000 (<0.1 percent) [1-3]. The specific mutations that an individual carries are a major determinant of clinical severity. The range of clinical expression likely reflects the degree to which protein function is changed by the mutation, modulation of the phenotype by other genes, and variation in susceptibility to environmental factors. (See "Cystic fibrosis: Genetics and pathogenesis".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- www.acmg.net (Accessed on March 24, 2009).
- Cystic Fibrosis Mutation Database. www.genet.sickkids.on.ca/cftr/ (Accessed on March 23, 2009).
- https://www.genetests.org/ (Accessed on September 17, 2015).
- Kerem B, Chiba-Falek O, Kerem E. Cystic fibrosis in Jews: frequency and mutation distribution. Genet Test 1997; 1:35.
- Shoshani T, Augarten A, Gazit E, et al. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet 1992; 50:222.
- Comeau AM, Accurso FJ, White TB, et al. Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report. Pediatrics 2007; 119:e495.
- Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med 2004; 6:387.
- Dodge JA, Lewis PA, Stanton M, Wilsher J. Cystic fibrosis mortality and survival in the UK: 1947-2003. Eur Respir J 2007; 29:522.
- Langfelder-Schwind E, Karczeski B, Strecker MN, et al. Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns 2014; 23:5.
- Committee on Genetics. Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol 2017; 129:e41.
- Duguépéroux I, Scotet V, Audrézet MP, et al. Nonvisualization of fetal gallbladder increases the risk of cystic fibrosis. Prenat Diagn 2012; 32:21.
- Strom CM, Crossley B, Buller-Buerkle A, et al. Cystic fibrosis testing 8 years on: lessons learned from carrier screening and sequencing analysis. Genet Med 2011; 13:166.
- Rohlfs EM, Zhou Z, Heim RA, et al. Cystic fibrosis carrier testing in an ethnically diverse US population. Clin Chem 2011; 57:841.
- Elias S, Annas GJ, Simpson JL. Carrier screening for cystic fibrosis: implications for obstetric and gynecologic practice. Am J Obstet Gynecol 1991; 164:1077.
- Castellani C, Picci L, Tamanini A, et al. Association between carrier screening and incidence of cystic fibrosis. JAMA 2009; 302:2573.
- Benn P. Non-Invasive Prenatal Testing Using Cell Free DNA in Maternal Plasma: Recent Developments and Future Prospects. J Clin Med 2014; 3:537.
- Kerem E, Corey M, Kerem BS, et al. The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med 1990; 323:1517.
- Kerem E, Reisman J, Corey M, et al. Prediction of mortality in patients with cystic fibrosis. N Engl J Med 1992; 326:1187.
- Cystic Fibrosis Genotype-Phenotype Consortium. Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993; 329:1308.
- Ferrari M, Cremonesi L. Genotype-phenotype correlation in cystic fibrosis patients. Ann Biol Clin (Paris) 1996; 54:235.
- Nishida K, Smith Z, Rana D, et al. Cystic fibrosis: a look into the future of prenatal screening and therapy. Birth Defects Res C Embryo Today 2015; 105:73.
- CF MUTATIONS
- CFTR mutation prevalence
- BENEFITS AND LIMITATIONS OF SCREENING
- CANDIDATES FOR SCREENING
- CARRIER TEST SELECTION
- Standard panel
- Expanded panel
- CFTR sequencing
- SCREENING STRATEGIES
- Couples with no personal or family history of CF
- Couples with a personal or family history of CF
- Father unavailable
- TEST REQUISITION
- TEST PERFORMANCE
- INTERPRETATION OF SCREENING RESULTS
- Positive screen
- Negative screen
- Genetic consultation
- REPRODUCTIVE OPTIONS FOR CARRIER COUPLES
- Noncarrier gamete donor
- Preimplantation genetic diagnosis
- Prenatal diagnosis
- - Chorionic villus sampling and amniocentesis
- - Noninvasive prenatal diagnosis
- - Prediction of phenotype
- PREGNANCY AND PERIPARTUM MANAGEMENT
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS