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Presymptomatic Genetic Testing: Shifting the Emphasis from Reaction to Prevention

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Molecular Genetics and Personalized Medicine

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

Presymptomatic genetic testing refers to genetic analysis of healthy individuals who are at increased risk for a specific heritable disorder, with the aim of predicting their likelihood to develop disease symptoms. At-risk individuals are usually identified because of a positive family history for a particular genetic condition. Presymptomatic testing differs from diagnostic genetic testing in that the information obtained is used to determine future health status rather than to confirm a diagnosis based on current clinical manifestations. This type of genetic testing is readily available for many disorders (Table 6.1), including adult-onset conditions and cancer predisposition syndromes.

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References

  1. Almqvist EW, Bloch M, Brinkman R, Craufurd D, Hayden MR. A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. Am J Hum Genet. 1999;64(5):1293–304.

    Article  PubMed  CAS  Google Scholar 

  2. Wexler NS. Huntington’s disease and other late onset genetic disorders. In: Emery A, Pullen G, editors. Psychological aspects of genetic counseling. New York: Academic Press, Inc.; 1984. p. 125–46.

    Google Scholar 

  3. Huntington G. On chorea. J Neuropsychiatry Clin Neurosci. 2003;15(1):109–12.

    Article  PubMed  Google Scholar 

  4. Harper PS. The epidemiology of Huntington’s disease. In: Bates G, Harper PS, Johnes L, editors. Huntington’s disease. 3rd ed. Oxford: Oxford University Press; 2002.

    Google Scholar 

  5. Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306(5940):234–8.

    Article  PubMed  CAS  Google Scholar 

  6. Macdonald M, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993;72(6):971–83.

    Article  Google Scholar 

  7. Warby SC, Graham RK, Hayden MR. 2010 Huntington disease. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997–2011. Available at http://www.genetests.org Accessed May 13, 2011.

    Google Scholar 

  8. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group. ACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic testing. Am J Hum Genet. 1998;62(5):1243–7.

    Article  Google Scholar 

  9. International Huntington Association and the World Federation of Neurology Research Group on Huntington’s Chorea. Guidelines for the molecular genetics predictive test in Huntington’s disease. J Med Genet. 1994;31(7):555–9.

    Google Scholar 

  10. Dufrasne S, Roy M, Galvez M, Rosenblatt DS. Experience over fifteen years with a protocol for predictive testing for Huntington disease. Mol Genet Metab. 2011;102(4):494–504.

    Article  PubMed  CAS  Google Scholar 

  11. Powell LW, George DK, McDonnell SM, Kowdley KV. Diagnosis of hemochromatosis. Ann Intern Med. 1998;129(11):925–31.

    PubMed  CAS  Google Scholar 

  12. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. 1996;110(4):1107–19.

    Article  PubMed  CAS  Google Scholar 

  13. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996;13(4):399–408.

    Article  PubMed  CAS  Google Scholar 

  14. Waheed A, Parkkila S, Zhou XY, et al. Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci USA. 1997;94(23):12384–9.

    Article  PubMed  CAS  Google Scholar 

  15. Burke W, Thomson E, Khoury MJ, et al. Hereditary hemochromatosis: gene discovery and its implications for population-based screening. JAMA. 1998;280(2):172–8.

    Article  PubMed  CAS  Google Scholar 

  16. Mura C, Raguenes O, Scotet V, Jacolot S, Mercier AY, Ferec C. A 6-year survey of HFE gene test for hemochromatosis diagnosis. Genet Med. 2005;7(1):68–73.

    Article  PubMed  CAS  Google Scholar 

  17. Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology. 2002;122(3):646–51.

    Article  PubMed  CAS  Google Scholar 

  18. Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T. Penetrance of 845G–>A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002;359(9302):211–8.

    Article  PubMed  Google Scholar 

  19. Loreal O, Deugnier Y, Moirand R, et al. Liver fibrosis in genetic hemochromatosis. Respective roles of iron and non-iron-related factors in 127 homozygous patients. J Hepatol. 1992;16(1–2):122–7.

    Article  PubMed  CAS  Google Scholar 

  20. Piperno A, Fargion S, D’Alba R, et al. Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection. J Hepatol. 1992;16(3):364–8.

    Article  PubMed  CAS  Google Scholar 

  21. Rochette J, Le Gac G, Lassoued K, Ferec C, Robson KJ. Factors influencing disease phenotype and penetrance in HFE haemochromatosis. Hum Genet. 2010;128(3):233–48.

    Google Scholar 

  22. Carayol J, Khlat M, Maccario J, Bonaiti-Pellie C. Hereditary non-polyposis colorectal cancer: current risks of colorectal cancer largely overestimated. J Med Genet. 2002;39(5):335–9.

    Article  PubMed  CAS  Google Scholar 

  23. Hampel H, Stephens JA, Pukkala E, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology. 2005;129(2):415–21.

    PubMed  Google Scholar 

  24. Vasen HF, Wijnen JT, Menko FH, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996;110(4):1020–7.

    Article  PubMed  CAS  Google Scholar 

  25. Watson P, Lynch HT. Cancer risk in mismatch repair gene mutation carriers. Fam Cancer. 2001;1(1):57–60.

    Article  PubMed  CAS  Google Scholar 

  26. Baglietto L, Lindor NM, Dowty JG, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193–201.

    Google Scholar 

  27. Dunlop MG, Farrington SM, Carothers AD, et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet. 1997;6(1):105–10.

    Article  PubMed  CAS  Google Scholar 

  28. Senter L, Clendenning M, Sotamaa K, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135(2):419–28.

    Article  PubMed  CAS  Google Scholar 

  29. Stoffel E, Mukherjee B, Raymond VM, et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology. 2009;137(5):1621–7.

    Article  PubMed  Google Scholar 

  30. Lynch HT, Krush AJ. Cancer family “G” revisited: 1895–1970. Cancer. 1971;27(6):1505–11.

    Article  PubMed  CAS  Google Scholar 

  31. Mecklin JP, Jarvinen HJ. Tumor spectrum in cancer family syndrome (hereditary nonpolyposis colorectal cancer). Cancer. 1991;68(5):1109–12.

    Article  PubMed  CAS  Google Scholar 

  32. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34(5):424–5.

    Article  PubMed  CAS  Google Scholar 

  33. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6.

    Article  PubMed  CAS  Google Scholar 

  34. Rodriguez-Bigas MA, Boland CR, Hamilton SR, et al. A National Cancer Institute Workshop on Hereditary Ponpolyposis Polorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst. 1997;89(23):1758–62.

    Article  PubMed  CAS  Google Scholar 

  35. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.

    Article  PubMed  CAS  Google Scholar 

  36. Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352(18):1851–60.

    Article  PubMed  CAS  Google Scholar 

  37. Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet. 2000;37(9):641–5.

    Article  PubMed  CAS  Google Scholar 

  38. Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. 2009;11(1):42–65.

    Article  PubMed  Google Scholar 

  39. Loukola A, Eklin K, Laiho P, et al. Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res. 2001;61(11):4545–9.

    PubMed  CAS  Google Scholar 

  40. Lindor NM, Petersen GM, Hadley DW, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA. 2006;296(12):1507–17.

    Article  PubMed  CAS  Google Scholar 

  41. Pino MS, Chung DC. Application of molecular diagnostics for the detection of Lynch syndrome. Expert Rev Mol Diagn. 2010;10(5):651–65.

    Google Scholar 

  42. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.

    Article  PubMed  CAS  Google Scholar 

  43. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002;418(6901):934.

    Article  PubMed  CAS  Google Scholar 

  44. Hitchins M, Williams R, Cheong K, et al. MLH1 germline epimutations as a factor in hereditary nonpolyposis colorectal cancer. Gastroenterology. 2005;129(5):1392–9.

    Article  PubMed  CAS  Google Scholar 

  45. Hitchins MP, Wong JJ, Suthers G, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med. 2007;356(7):697–705.

    Article  PubMed  CAS  Google Scholar 

  46. Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 2004;36(5):497–501.

    Article  PubMed  CAS  Google Scholar 

  47. Jarvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118(5):829–34.

    Article  PubMed  CAS  Google Scholar 

  48. Syngal S, Weeks JC, Schrag D, Garber JE, Kuntz KM. Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations. Ann Intern Med. 1998;129(10):787–96.

    PubMed  CAS  Google Scholar 

  49. Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612.

    Article  PubMed  Google Scholar 

  50. Skinner MA, DeBenedetti MK, Moley JF, Norton JA, Wells Jr SA. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg. 1996;31(1):177–81. discussion 181–172.

    Article  PubMed  CAS  Google Scholar 

  51. Erlic Z, Hoffmann MM, Sullivan M, et al. Pathogenicity of DNA variants and double mutations in multiple endocrine neoplasia type 2 and von Hippel-Lindau syndrome. J Clin Endocrinol Metab. 2009;95(1):308–13.

    Google Scholar 

  52. Margraf RL, Crockett DK, Krautscheid PM, et al. Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlations. Hum Mutat. 2009;30(4):548–56.

    Article  PubMed  CAS  Google Scholar 

  53. Rodriguez JM, Balsalobre M, Ponce JL, et al. Pheochromocytoma in MEN 2A syndrome. Study of 54 patients. World J Surg. 2008;32(11):2520–6.

    Article  PubMed  Google Scholar 

  54. Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H. Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene. 1988;3(5):571–8.

    PubMed  CAS  Google Scholar 

  55. Treanor JJ, Goodman L, de Sauvage F, et al. Characterization of a multicomponent receptor for GDNF. Nature. 1996;382(6586):80–3.

    Article  PubMed  CAS  Google Scholar 

  56. Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer. 2005;5(5):367–75.

    Article  PubMed  CAS  Google Scholar 

  57. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.

    Article  PubMed  CAS  Google Scholar 

  58. Borry P, Stultiens L, Nys H, Cassiman JJ, Dierickx K. Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers. Clin Genet. 2006;70(5):374–81.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA

    Irene H. Hung M.D. & John C. Carey M.D., M.P.H.

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  1. Irene H. Hung M.D.
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  2. John C. Carey M.D., M.P.H.
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Correspondence to Irene H. Hung M.D. .

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Editors and Affiliations

  1. , Department of Pathology, University of Utah School of Medicine, Salt Lake City, 84108, Utah, USA

    D. Hunter Best

  2. , Department of Pathology, University of Utah School of Medicine, Salt Lake City, 84108, Utah, USA

    Jeffrey J. Swensen

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Hung, I.H., Carey, J.C. (2012). Presymptomatic Genetic Testing: Shifting the Emphasis from Reaction to Prevention. In: Best, D., Swensen, J. (eds) Molecular Genetics and Personalized Medicine. Molecular and Translational Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-530-5_6

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  • DOI: https://doi.org/10.1007/978-1-61779-530-5_6

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