Cystic Fibrosis

  • Eugene H. LewisIII
  • Myra J. Lewis
  • Jean A. Amos
  • Gregory J. Tsongalis


Cystic fibrosis (CF), a clinically heterogeneous disease, is the first genetic disease for which adult population screening has been initiated in the United States. Since the discovery of the CFTR gene in 1989, much has been learned about the pathophysiology and molecular genetics of this disorder. This review includes an overview of the genetics of CF, a discussion of pathophysiology, and clinical and anatomic pathology and concludes with a review of molecular diagnostics.


Sweat Test Ical Membrane Cystic Fibrosis Genetic Analysis Consortium Reverse Line Probe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brennan, A. L., and Geddes, D. M. Cystic fibrosis. Curr. Opin. Infect. Dis.15:175–182, 2002.PubMedGoogle Scholar
  2. 2.
    Rommens, J. M., Iannuzzi, M. C., Kerem, B., et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245(4922):1059–1065, 1989.PubMedCrossRefGoogle Scholar
  3. 3.
    Riordan, J. R., Rommens, J. M., Kerem B., et al. Identification of the cystic fibrosis gene: cloning and characterization of complimen–tary DNA. Science 245(4922):1066–1073, 1989.PubMedCrossRefGoogle Scholar
  4. 4.
    Kerem, B., and Rommens, J. M., Buchanan, J. A., et al. Identification of the cystic fibrosis gene: genetic analysis. Science 245: 1073–1080, 1989.PubMedCrossRefGoogle Scholar
  5. 5.
    Rosenstein, B. J., and Zeitlin, P. L. Cystic fibrosis. Lancet 351: 277–282, 1998.PubMedCrossRefGoogle Scholar
  6. 6.
    The Cystic Fibrosis Genetic Analysis Consortium. Cystic Fibrosis Mut–ation Data Base. Available at
  7. 7.
    Vankeerberghen, A., Cuppens, H., and Cassiman, J. J. The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions. J. Cystic Fibrosis 1:13–29, 2002.CrossRefGoogle Scholar
  8. 8.
    Zielenski, J. Genotype and phenotype in cystic fibrosis. Respiration 67:117–133, 2000.PubMedCrossRefGoogle Scholar
  9. 9.
    The Cystic Fibrosis Genotype–phenotype Consortium.Correlation between genotype and phenotype in cystic fibrosis. N. Engl. J. Med. 329:1308–1313, 1993.CrossRefGoogle Scholar
  10. 10.
    Morral, N., Betranpetit, J., Estivill, X., et al. The origin of the major cystic fibrosis mutation (delta F508) in European populations. Nat. Genet 7:169–175, 1994.PubMedCrossRefGoogle Scholar
  11. 11.
    Wine, J. J. The genesis of cystic fibrosis lung disease. J. Clin. Invest.103(3):309–312, 1999.PubMedCrossRefGoogle Scholar
  12. 12.
    Bales, R., Weiner, D. J., and Wilson J. M. The innate immune system in cystic fibrosis lung disease. J. Clin. Invest. 103(3):303–307, 1999.CrossRefGoogle Scholar
  13. 13.
    Goldman, M. J., Anderson, G.M., Stolzenberg, E. D., et al. Human beta–defensin–1 is a salt –sensitive antibiotic in lung that is inacti–vated in cyctic fibrosis. Cell 88:553–560,1997.PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis, M. J., Lewis, E. H., III, Amos, J. A., and Tsongalis, G. J. Cystic fibrosis. Am. J. Clin. Pathol. Pathol. Patterns, 120 (suppl): s3–13, 2003.CrossRefGoogle Scholar
  15. 15.
    Cystic Fibrosis Foundation, Patient Registry. 2001 Annual Report. Cystic Fibrosis Foundation, Bethesda, MD, 2002.Google Scholar
  16. 16.
    Ratjen, F., and Doring, G. Cystic fibrosis. Lancet 361: 681–689, 2003.PubMedCrossRefGoogle Scholar
  17. 17.
    Sly, P. and Stick, S. Cystic fibrosis. Thorax 56(3):237–241, 2001.CrossRefGoogle Scholar
  18. 18.
    Reyes–Mugica, M. and Gonzalez–Crossi, F. Pulmonary disease in the pediatric age group, in Pathology of Pulmonary Disease, Saldana, M. J., ed., Lippincott, Philadelphia, pp. 93–99, 1994.Google Scholar
  19. 19.
    King, A., Mueller, R. F., Heeley, A. F., et al. Diagnosis of cystic fibrosis in premature infants. Pe diatr. Res. 20(6): 536–541, 1986.CrossRefGoogle Scholar
  20. 20.
    Liu, P., Daneman, A., Stringer, D. A., and Durie, P. R. Pancreatic cysts and calcification in cystic fibrosis. J. Can. Assoc. Radiol. 37(4):279–282, 1986.Google Scholar
  21. 21.
    Imrie, J., Fagan, D., and Sturgess, J. Quantitative evaluation of the development of the exocrine pancreas in CF and control infants. Am. J. Pathol. 95(3):697–707, 1979.PubMedGoogle Scholar
  22. 22.
    Kopelman, H. R., Durie, P., Gaskin, K. J., Weizman, Z., and Forstner, G. G. Pancreatic fluid and protein hyperconcentration in cystic fibrosis. N. Engl. J. Med. 312(6): 329–334,1985.PubMedCrossRefGoogle Scholar
  23. 23.
    Kopelman, H. R., Forstner, G. G., Durie, P., and Corey, M. Origins of chloride and bicarbonate secretory defect in the cystic fibrosis pancreas as suggested by pancreatic function studies in control and CF subjects with preserved pancreatic function. Clin. Invest. Med. 12(3): 207–211, 1989.PubMedGoogle Scholar
  24. 24.
    Durie, P. R., and Forstner, G. G. The exocrine pancreas, in Cystic Fibrosis in Adults. Lippencott–Raven, Philadelphia, PA, pp. 261–287, 1999.Google Scholar
  25. 25.
    O’Brien, S., Keogan, M., Casey, M., et al. Biliary complications of cystic fibrosis. Gut 33:387–391, 1992.PubMedCrossRefGoogle Scholar
  26. 26.
    Modolell, I., Guarner, L., and Malagelada, J. R. Digestive system involvement in cystic fibrosis. Pancreatlolgy 2:12–16, 2002.CrossRefGoogle Scholar
  27. 27.
    Scott–Jupp, R., Lama, M., and Tanner, M. S. Prevalence of liver dis–ease in cystic fibrosis. Arch. Dis. Child. 66:698–701, 1991.PubMedCrossRefGoogle Scholar
  28. 28.
    Colombo, C., Battezzati, P. M., and Podda, M. Hepatobiliary dis–ease in cystic fibrosis. Semin. Liver Dis. 14:259–269, 1994.PubMedCrossRefGoogle Scholar
  29. 29.
    Cannon, J. J. Gallbladder and biliary tract disease in cystic fibrosis. Semin. Liver Dis. 14:259–269, 1994.CrossRefGoogle Scholar
  30. 30.
    Strandvik, B., Hjelte, L., Gabrielson, N., et al. Sclerosing cholangitis in cystic fibrosis. Scand. J. Gastroenterol. 23(Suppl.143):121–124, 1998.CrossRefGoogle Scholar
  31. 31.
    Isenberg, J. N. Cystic fibrosis: its influence on the liver, biliary tree, and bile salt metabolism. Semin. Liver Dis. 2:302–313, 1982.PubMedCrossRefGoogle Scholar
  32. 32.
    Lambert, J. R., Cole, M., Crozier, D. N., and Cannon, J. J. Intra pan–creatic common bile duct compression causing jaundice in an adult with cystic fibrosis. Gastroenterology 80:169–172, 1981.PubMedGoogle Scholar
  33. 33.
    Strandvik, B., Hjelte, L., Gabrielson, N., and Glaumann, H. Sclerosing cholangitis in cystic fibrosis. Scand. J. Gastroenterol. 143(Suppl):121–124, 1988.CrossRefGoogle Scholar
  34. 34.
    Stern, R. C., Rothstein, F. C., and Doershuk, C. F. Treatment and prognosis of symptomatic gallbladder disease in patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nut 5:35–40, 1986.CrossRefGoogle Scholar
  35. 35.
    Colombo, C., Apostolo, M. J., Ferrari, M., et al. Analysis of risk fac–tors for the development of liver disease associated with cystic fibrosis. J. Pediatr 124:129–132, 1994.Google Scholar
  36. 36.
    Hausler, M., Heimann, G., and Biesterfeld, S. Fibrosis: a general feature in cystic fibrosis? J. Pediatr. Gastroenterol. Nut 34:236–239, 2002.CrossRefGoogle Scholar
  37. 37.
    Rubenstein, S., Moss, R., and Lewiston, N. Constipation and meco–nium ileus equivalent in patients with cystic fibrosis. Pediatrics 78:473–479, 1986.Google Scholar
  38. 38.
    Pawel, B. R., Chadarevian, J. P., and Franco, M. E. The pathology of fibrosing colonopathy of cystic fibrosis: a study of 12 cases and review of the literature. Hum. Pathol. 28:395–399, 1997.PubMedCrossRefGoogle Scholar
  39. 39.
    Smyth, R. L., Ashby, D., O’Hea, U., et al. Fibrosing colonopathy in cystic fibrosis: results of a case–control study. Gastroenterlogy 111:260–264, 1996.CrossRefGoogle Scholar
  40. 40.
    Lewis, T. C., Casey, S. C., and Kapur, R. P. Clinical pathologic correlation: a 3–year old boy with cystic fibrosis and intestinal obstruc–tion. J. Pediatr. 134:514–519, 1999.PubMedCrossRefGoogle Scholar
  41. 41.
    Milla, P. J. Cystic fibrosis: present and future. Digestion 59: 579–588, 1998.PubMedCrossRefGoogle Scholar
  42. 42.
    Bourke, S., Rooney, M., Fitzgerald, M., et al. Episodic arthropathy in adult cystic fibrosis. Q. J. Med. 244:651–659, 1987.Google Scholar
  43. 43.
    Johnson, S., and Knox, A. J. Arthropathy in cystic fibrosis. Respir. Med. 88:567–570, 1994.PubMedCrossRefGoogle Scholar
  44. 44.
    Newman, A. J., and Ansell, B. A. Episodic arthritis in children with cystic fibrosis. J. Pediatr. 94:594–596, 1979.PubMedCrossRefGoogle Scholar
  45. 45.
    Schidlow, D.V., Goldsmith, D. P., Palmer, J., et al. Arthritis in cystic fibrosis. Arch. Dis. Child. 59:377–379, 1984.PubMedCrossRefGoogle Scholar
  46. 46.
    Turner, M. A., Baildam, E., Patel, L., et al. Joint disorders in cystic fibrosis. J. R. Soc. Med. 90(Suppl. 31):13–20, 1997.PubMedGoogle Scholar
  47. 47.
    Pertuiset, E., Menkes, C. J., Lenoir G., et al. Cystic fibrosis arthri–tis. A report of five cases. B r. J. Rheumatol. 31:535–538, 1992.PubMedCrossRefGoogle Scholar
  48. 48.
    Phillips, B.M., and David, T. J. Pathogenesis and management of arthropathy in cystic fibrosis. J. R. Soc. Med. 79(Suppl.12):44–50, 1986.PubMedGoogle Scholar
  49. 49.
    Dodge, J. A. Male fertility in cystic fibrosis. Lancet 346:587–588, 1995.PubMedCrossRefGoogle Scholar
  50. 50.
    Chillon, M., Casals, T., Mercier, B., et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N. Engl. J. Med. 332:1475–1480, 1995.PubMedCrossRefGoogle Scholar
  51. 51.
    Robert, S. C. Current concepts: the diagnosis of cystic fibrosis. N. Engl. J. Med. 336:487–491, 1997.CrossRefGoogle Scholar
  52. 52.
    Kopito, L. E., Kosasky, H. J., and Shwahman, H. Water and elec–trolytes in cervical mucus from patients with cystic fibrosis. Fe rtil. Steril. 24:512–516, 1973.Google Scholar
  53. 53.
    Ratjen, F., and Doring, G. Cystic fibrosis. Lancet 361:681–689, 2003.PubMedCrossRefGoogle Scholar
  54. 54.
    Finnegan, M. J., Hinchcliffe, J., Russell–Jones, D., et al. Vasculitis complicating cystic fibrosis. Q. J. Med. 267:609–621, 1989.Google Scholar
  55. 55.
    Richards, C. S., Bradley, L. A., Amos, J., et al. Standards and guide–lines for CFTR mutation testing. Genet. Med 4:379–391, 2002.PubMedCrossRefGoogle Scholar
  56. 56.
    Preconception and prenatal carrier screening for cystic fibrosis. American College of Obstetricians and Gynecologists/American College of Medical Genetics. 2001, pp.1–31.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Eugene H. LewisIII
    • 1
  • Myra J. Lewis
    • 1
  • Jean A. Amos
    • 2
  • Gregory J. Tsongalis
    • 3
  1. 1.Department of Pathology and Laboratory MedicineHartford HospitalHartfordUSA
  2. 2.Molecular GeneticsSpecialty Laboratorie, Inc.Santa Monica
  3. 3.Department of PathologyDartmouth Medical School, Dartmouth-Hitchcock Medical CenterLebanon

Personalised recommendations