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Molecular Testing for Cystic Fibrosis Carrier Status Practice Guidelines: Recommendations of the National Society of Genetic Counselors

  • Professional Issues
  • Published:
Journal of Genetic Counseling

Purpose

To provide practice recommendations for genetic counselors whose clients are considering cystic fibrosis (CF) carrier testing or seeking information regarding CF molecular test results. The goals of these recommendations are to: 1) Provide updated information about the natural history, diagnosis, and treatment of CF and related conditions. 2) Supplement genetic counselors’ knowledge and understanding of the available carrier screening and diagnostic testing options. 3) Describe the current state of genotype/phenotype correlations for CFTR mutations and an approach to interpreting both novel and previously described variants. 4) Provide a framework for genetic counselors to assist clients’ decision-making regarding CF carrier testing, prenatal diagnosis, and pregnancy management.

Disclaimer The practice guidelines of the National Society of Genetic Counselors (NSGC) are developed by members of the NSGC to assist genetic counselors and other health care providers in making decisions about appropriate management of genetic concerns; including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue, and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the NSGC practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are only current as of their publication date, and are subject to change without notice as advances emerge.

In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health care provider’s best medical judgment based on the clinical circumstances of a particular patient or patient population.

Practice guidelines are published by NSGC for educational and informational purposes only, and NSGC does not “approve” or “endorse” any specific methods, practices, or sources of information.

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References

  • American College of Obstetricians and Gynecologists. (2005). Update on carrier screening for cystic fibrosis Committee Opinion No. 325. Obstetrics and Gynecology, 106(6), 1465–1468.

    Article  Google Scholar 

  • American College of Obstetricians and Gynecologists. (2011). Update on carrier screening for cystic fibrosis. Committee Opinion No. 486. Obstetrics and Gynecology, 117(4), 1028–1031.

    Article  Google Scholar 

  • American College of Obstetricians and Gynecologists, & American College of Medical Genetics. (2001). Preconception and prenatal carrier screening for cystic fibrosis. Clinical and Laboratory Guidelines. American College of Obstetricians and Gynecologists, Washington, DC.

  • Bobadilla, J. L., Macek, M., Jr., Fine, J. P., & Farrell, P. M. (2002). Cystic fibrosis: a worldwide analysis of CFTR mutations– correlation with incidence data and application to screening. Human Mutation, 19(6), 575–606.

    Article  CAS  PubMed  Google Scholar 

  • Bombieri, C., Claustres, M., De Boeck, K., et al. (2011). Recommendations for the classification of diseases as CFTR-related disorders. Journal of Cystic Fibrosis, 10(Suppl2), S86–S102.

    Article  CAS  PubMed  Google Scholar 

  • Borowitz, D., Parad, R., Sharp, J. K., et al. (2009). Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome during the first two years of life and beyond. Journal of Pediatrics, 155, S106e16.

    Google Scholar 

  • Buller, A., Olson, S., Redman, J. B., et al. (2004). Frequency of the cystic fibrosis 3199del6 mutation in individuals heterozygous for I148T. Genetics in Medicine, 6(2), 108–109.

    Article  CAS  PubMed  Google Scholar 

  • Carlyle, B. E., Borowitz, D. S., & Glick, P. L. (2012). A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon. Journal of Pediatric Surgery, 47(4), 772–781.

    Article  PubMed  Google Scholar 

  • Castellani, C., Cuppens, H., Macek, M., et al. (2008). Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. Journal of Cystic Fibrosis, 7, 179–196.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Claustres, M., Altiére, J.-P., Guittard, C., et al. (2004). Are p.I148T, p.R74W and p.D1270N cystic fibrosis causing mutations? BMC Medical Genetics, 5, 19.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cleveland, R. H., Zurakowski, D., Slattery, D., & Colin, A. A. (2009). Cystic fibrosis genotype and assessing rates of decline in pulmonary status. Radiology, 253(3), 813–821.

    Article  PubMed  Google Scholar 

  • Collaco, J. M., & Cutting, G. R. (2008). Update on gene modifiers in cystic fibrosis. Current Opinion in Pulmonary Medicine, 14(6), 559–566.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cuppens, H., Lin, W., Jaspers, M., Costes, B., Teng, H., Vankeerberghen, A., et al. (1998). Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. Journal of Clinical Investigation, 101(2), 487–496.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cystic Fibrosis Foundation. (1997). Clinical practice guidelines.

  • Cystic Fibrosis Foundation Patient Registry. (2011). Database, accessed 24 April 2013. Bethesda, Maryland.

  • Cystic Fibrosis Foundation Patient Registry. (2012). 2011 Annual data report.

  • De Boeck, K., Wilschanski, M., Castellani, C., et al. (2006). Cystic fibrosis: terminology and diagnostic algorithms. Thorax, 61, 627–635.

    Article  PubMed  Google Scholar 

  • Dequeker, E., Stuhrmann, M., Morris, M. A., et al. (2009). Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders—updated European recommendations. European Journal of Human Genetics, 17(1), 51–65.

    Article  CAS  PubMed  Google Scholar 

  • Di Sant’Agnese, P. A., Darling, R. C., Perera, G. A., & Shea, E. (1953). Sweat electrolyte disturbances associated with childhood pancreatic disease. American Journal of Medicine, 15(6), 777–784.

    Article  Google Scholar 

  • Drumm, M. L., Konstan, M. W., Schluchter, M. D., Handler, A., Pace, R., Zou, F., et al. (2005). Gene Modifier Study Group. New England Journal of Medicine, 353(14), 1443–1453.

    Google Scholar 

  • Eshaque, B., & Dixon, B. (2006). Technology platforms for molecular diagnosis of cystic fibrosis. Biotechnology Advances, 24, 86–93.

    Article  CAS  PubMed  Google Scholar 

  • Farrell, P. M., Kosorok, M. R., Laxova, A., et al. (1997). Wisconsin Cystic Fibrosis Neonatal Screening Study Group. Nutritional benefits of neonatal screening for cystic fibrosis. The New England Journal of Medicine, 337, 963–969.

    Article  CAS  PubMed  Google Scholar 

  • Farrell, P. M., Rosenstein, B. J., White, T. B., et al. (2008). Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. Journal of Pediatrics, 15(3), S4–S14.

    Article  Google Scholar 

  • Fiel, S. B. (1996). Pulmonary function during pregnancy in cystic fibrosis: implications for counseling. Current Opinion in Pulmonary Medicine, 2(6), 462–465.

    CAS  PubMed  Google Scholar 

  • Grody, W. W., Cutting, G. R., Klinger, K. W., et al. (2001). Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genetics in Medicine, 3(2), 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Grody, W. W., Cutting, G. R., & Watson, M. S. (2007). The cystic fibrosis mutation “arms race”: when less is more. Genetics in Medicine, 9(11), 739–744.

    Article  PubMed  Google Scholar 

  • Groman, J. D., Karczeski, B., Sheridan, M., et al. (2005). Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosis. Journal of Pediatrics, 146(5), 675–680.

    Article  PubMed Central  PubMed  Google Scholar 

  • Groman, J. D., Hefferon, T. W., Casals, T., et al. (2004). Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. American Journal of Human Genetics, 74(1), 176–179.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Howenstine, M., & Montegomery, G. S. (2009). Cystic fibrosis. Pediatrics in Review, 30, 302–310. doi:10.1542/pir.30-8-302.

    Article  PubMed  Google Scholar 

  • Jones, A. M., & Helm, J. M. (2009). Emerging treatments in cystic fibrosis. Drugs, 69(14), 1903–1910.

    Article  CAS  PubMed  Google Scholar 

  • Keiles, S., Koepke, R., Parad, R., et al. (2011). Impact of IVS8-(TG)m(T)n on IRT and sweat chloride levels in newborns identified by California CF newborn screening. Journal of Cystic Fibrosis (in press).

  • Kere, E., Reisman, J., Corey, M., et al. (1992). Prediction of mortality in patients with cystic fibrosis. New England Journal of Medicine, 326(8), 1187–1191.

    Article  Google Scholar 

  • Kiesewetter, S., Macek, M., Jr., Davis, C., et al. (1993). A mutation in CFTR produces different phenotypes depending on chromosomal background. Nature Genetics, 5(3), 274–278.

    Article  CAS  PubMed  Google Scholar 

  • Koscik, R. L., Lai, H., Laxova, A., et al. (2005). Preventing early, prolonged vitamin E deficiency: an opportunity for better cognitive outcomes via early diagnosis through neonatal screening. Journal of Pediatrics, 147(3 Suppl), S51–S56.

    Article  PubMed  Google Scholar 

  • Langfelder-Schwind, E., Kloza, E., Sugarman, E., et al. (2005). Cystic fibrosis prenatal screening in genetic counseling practice: recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 14(1), 1–15.

    Article  PubMed  Google Scholar 

  • Lebo, R. V., & Grody, W. W. (2007). Testing and reporting ACMG cystic fibrosis mutation panel results. Genetic Testing, 11(1), 11–31.

    Article  CAS  PubMed  Google Scholar 

  • Massie, R. J., Poplawski, N., Wilcken, B., et al. (2001). Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C. European Respiratory Journal, 17(6), 1195–1200.

    Article  CAS  PubMed  Google Scholar 

  • Massie, R. J. H., Curnow, L., Glazner, J., et al. (2012). Lessons learned from 20 years of newborn screening for cystic fibrosis. The Medical Journal of Australia, 196(1), 67–70.

    Article  PubMed  Google Scholar 

  • McKone, E. F., Emerson, S. S., Edwards, K. L., & Aitken, M. L. (2003). Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet, 361(9370), 1671–1676.

    Article  CAS  PubMed  Google Scholar 

  • McKone, E. F., Goss, C. H., & Aitken, M. L. (2006). CFTR genotype as a predictor of prognosis in cystic fibrosis. Chest, 130(5), 1441–1447.

    Article  PubMed  Google Scholar 

  • Mehta, G., Macek, M., Jr., Mehta, A., & European Registry Working Group. (2010). Cystic fibrosis across Europe: EuroCareCF analysis of demographic data from 35 countries. Journal of Cystic Fibrosis, 9(Suppl 2), S5–S21.

    Article  PubMed  Google Scholar 

  • Mérelle, M. E., Scheffer, H., DeJong, D., & Dankert-Roelse, J. E. (2006). Extended gene analysis can increase specificity of neonatal screening for cystic fibrosis. Acta Paediatrica, 95, 1424–1428.

    Article  PubMed  Google Scholar 

  • Mickle, J. E., & Cutting, G. R. (1998). Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clinics in Chest Medicine, 19(3), 443–458.

    Article  CAS  PubMed  Google Scholar 

  • Monaghan, K. G., Highsmith, W. E., Amos, J., et al. (2004). Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study. Genetics in Medicine, 6(5), 421–425.

    Article  CAS  PubMed  Google Scholar 

  • Moran, A., Brunzell, C., Cohen, R. C., et al. (2010). CFRD Guidelines Committee. Clinical care guidelines for cystic fibrosis-related diabetes. Diabetes Care, 33(12), 2697–2708.

    Article  PubMed  Google Scholar 

  • Morton, J., & Glanville, A. R. (2009). Lung transplantation in patients with cystic fibrosis. Seminars in Respiratory and Critical Care Medicine, 30(5), 559–568.

    Article  PubMed  Google Scholar 

  • Moskowitz, S. M., Chmiel, J. F., Sternen, D. L., et al. (2008). Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders. Genetics in Medicine, 10(12), 851–868.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mussaffi, H., Prais, D., Mei-Zahav, M., & Blau, H. (2006). Cystic fibrosis mutations with widely variable phenotype: the D1152H example. Pediatric Pulmonology, 41(3), 250–254.

    Article  CAS  PubMed  Google Scholar 

  • Ogino, S., Wilson, R. B., & Grody, W. W. (2004). Bayesian risk assessment for autosomal recessive diseases: fetal echogenic bowel with one or not detectable CFTR mutation. Journal of Medical Genetics, 41(5), e70.

    Article  CAS  PubMed  Google Scholar 

  • O’Neill, S. C., DeMarco, T., Peshkin, B. N., et al. (2006). Tolerance for uncertainty and perceived risk among women receiving uninformative BRCA1/2 test results. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 142C(4), 251–259.

    Article  PubMed  Google Scholar 

  • Palomaki, G. E., FitzSimmons, S. C., & Haddow, J. E. (2004). Clinical sensitivity of prenatal screening for cystic fibrosis via CFTR carrier testing in a United States panethnic population. Genetics in Medicine, 6(5), 405–414.

    Article  PubMed  Google Scholar 

  • Quittner, A. L., Modi, A., & Cruz, I. (2008). Systematic review of health-related quality of life measures for children with respiratory conditions. Paediatric Respiratory Reviews, 9(3), 220–232.

    Article  PubMed  Google Scholar 

  • Rohlfs, E. M., Sugarman, E. A., Heim, R. A., & Allitto, B. A. (2001). Frequency of carriers of two cystic fibrosis mutations in an apparently unaffected adult population. Genetics in Medicine, 3, 237.

    Google Scholar 

  • Rohlfs, E. M., Zhou, Z., Sugarman, E. A., et al. (2002). The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis. Genetics in Medicine, 4(5), 319–323.

    Article  CAS  PubMed  Google Scholar 

  • Rohlfs, E. M., Zhou, Z., Heim, R. A., et al. (2011). Cystic fibrosis carrier testing in an ethnically diverse US population. Clinical Chemistry, 57(6), 841–848.

    Article  CAS  PubMed  Google Scholar 

  • Rosenstein, B. J., & Cutting, G. R. (1998). The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation consensus panel. Journal of Pediatrics, 132(4), 589–595.

    Article  CAS  PubMed  Google Scholar 

  • Sawicki, G. S., Rasouliyan, L., McMullen, A. H., et al. (2010). Longitudinal assessment of health-related quality of life in an observational cohort of patients with cystic fibrosis. Pediatric Pulmonology, 46(1), 36–44.

    Article  PubMed  Google Scholar 

  • Schibli, S., Durie, P. R., & Tullis, E. D. (2002). Proper usage of pancreatic enzymes. Current Opinion in Pulmonary Medicine, 8, 542–546.

    Article  PubMed  Google Scholar 

  • Schlegel, P. N., Cohen, J., Goldstein, M., et al. (1995). Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens. Fertility and Sterility, 64(2), 421–426.

    CAS  PubMed  Google Scholar 

  • Sebro, R., Levy, H., Schneck, K., et al. (2012). Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency. Clinical Genetics, 82, 546–551.

    Article  CAS  PubMed  Google Scholar 

  • Smith, H. C. (2010). Fertility in men with cystic fibrosis assessment, investigations and management. Paediatric Respiratory Reviews, 11(2), 80–83.

    Article  PubMed  Google Scholar 

  • Sosnay, P. R., Castellani, C., Corey, M., et al. (2011). Evaluation of the disease liability of CFTR variants. Methods in Molecular Biology, 742, 355–372.

    Article  CAS  PubMed  Google Scholar 

  • Strom, C. M., Huang, D., Chen, C., et al. (2003). Extensive sequencing of the cystic fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a comprehensive test. Genetics in Medicine, 5(1), 9–14.

    Article  CAS  PubMed  Google Scholar 

  • Svensson, A. M., Chou, L. S., Miller, C. E., et al. (2010). Detection of large rearrangements in the cystic fibrosis transmembrane conductance regulator gene by multiplex ligation-dependent probe amplification assay when sequencing fails to detect two disease-causing mutations. Genetic Testing and Molecular Biomarkers, 14(2), 171–174.

    Article  CAS  PubMed  Google Scholar 

  • Taylor, C. J., Hardcastle, J., & Southern, K. W. (2009). Physiological measurements confirming the diagnosis of cystic fibrosis: the sweat test and measurements of transepithelial potential difference. Paediatric Respiratory Reviews, 10(4), 220–226.

    Article  CAS  PubMed  Google Scholar 

  • Thauvin-Robinet, C., Munck, A., Huet, F., et al. (2009). Collaborating Working Group on R117H. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counseling and newborn screening. Journal of Medical Genetics, 46(11), 752–758.

    Article  CAS  PubMed  Google Scholar 

  • Tluczek, A., Zaleski, C., Stachiw-Hietpas, D., et al. (2011). A tailored approach to family-centered genetic counseling for cystic fibrosis newborn screening: the Wisconsin model. Journal of Genetic Counseling, 20(2), 115–128.

    Article  PubMed Central  PubMed  Google Scholar 

  • Uhlmann, W. (2009). Thinking it all through: Case preparation and management. In D. L. Baker, J. L. Schuette, & W. Uhlmann (Eds.), A guide to genetic counseling (2nd ed., pp. 108–110). New York: Wiley-Liss, Inc.

    Google Scholar 

  • Vanscoy, L. L., Blackman, S. M., Collaco, J. M., Bowers, A., Lai, T., Naughton, K., et al. (2007). American Journal of Respiratory and Critical Care Medicine, 175(10), 1036–1043.

    Article  CAS  PubMed  Google Scholar 

  • Waters, D. L., Wilcken, B., Irwig, L., et al. (1999). Clinical outcomes of newborn screening for cystic fibrosis. Archives of Disease in Childhood. Fetal and Neonatal Edition, 80(1), F1–F7.

    Article  CAS  PubMed  Google Scholar 

  • Watson, M. S., Cutting, G. R., Desnick, R. J., et al. (2004). Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genetics in Medicine, 6(5), 387–391.

    Article  PubMed Central  PubMed  Google Scholar 

  • Weil, J. (Ed.). (2000). Psychosocial genetic counseling (pp. 133–134). New York: Oxford University Press.

    Google Scholar 

  • Zielenski, J. (2000). Genotype and phenotype in cystic fibrosis. Respiration, 67(2), 117–133.

    Article  CAS  PubMed  Google Scholar 

  • Whittey, J. E. (2010). Cystic fibrosis in pregnancy. Clinical Obstetrics and Gynecology, 53(2), 369–376.

    Article  Google Scholar 

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Authors and Affiliations

  1. Beth Israel Medical Center, New York, NY, USA

    Elinor Langfelder-Schwind

  2. DNA Diagnostic Laboratory, Johns Hopkins University, Baltimore, MD, USA

    Barbara Karczeski

  3. CombiMatrix Diagnostics, Irvine, CA, USA

    Michelle N. Strecker

  4. Quest Diagnostics, San Juan Capistrano, CA, USA

    Joy Redman

  5. Integrated Genetics, Westborough, MA, USA

    Elaine A. Sugarman

  6. Marshfield Clinic, Marshfield, WI, USA

    Christina Zaleski

  7. Prevention Genetics, Marshfield, WI, USA

    Christina Zaleski

  8. Shama Consulting, Clayton, CA, USA

    Trisha Brown

  9. Ambry Genetics, Aliso Viejo, CA, USA

    Steven Keiles

  10. University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA

    Amy Powers

  11. St. Vincent’s Hospital, Green Bay, WI, USA

    Sumheda Ghate

  12. Case Western Reserve University, Cleveland, OH, USA

    Rebecca Darrah

Authors
  1. Elinor Langfelder-Schwind
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  2. Barbara Karczeski
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  3. Michelle N. Strecker
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  4. Joy Redman
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  5. Elaine A. Sugarman
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  6. Christina Zaleski
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  7. Trisha Brown
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  8. Steven Keiles
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  9. Amy Powers
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  10. Sumheda Ghate
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  11. Rebecca Darrah
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Correspondence to Elinor Langfelder-Schwind.

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Langfelder-Schwind, E., Karczeski, B., Strecker, M.N. et al. Molecular Testing for Cystic Fibrosis Carrier Status Practice Guidelines: Recommendations of the National Society of Genetic Counselors. J Genet Counsel 23, 5–15 (2014). https://doi.org/10.1007/s10897-013-9636-9

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  • DOI: https://doi.org/10.1007/s10897-013-9636-9

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