Skip to main content
SpringerLink
Log in

The influence of PRNP polymorphisms on human prion disease susceptibility: an update

  • Review
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Two normally occurring polymorphisms of the human PRNP gene, methionine (M)/valine (V) at codon 129 and glutamic acid (E)/lysine (K) at codon 219, can affect the susceptibility to prion diseases. It has long been recognized that 129M/M homozygotes are overrepresented in sporadic Creutzfeldt–Jakob disease (CJD) patients and variant CJD patients, whereas 219E/K heterozygotes are absent in sporadic CJD patients. In addition to these pioneering findings, recent progress in experimental transmission studies and worldwide surveillance of prion diseases have identified novel relationships between the PRNP polymorphisms and the prion disease susceptibility. For example, although 219E/K heterozygosity confers resistance against the development of sporadic CJD, this genotype is not entirely protective against acquired forms (iatrogenic CJD and variant CJD) or genetic forms (genetic CJD and Gerstmann–Sträussler–Scheinker syndrome) of prion diseases. In addition, 129M/V heterozygotes predispose to genetic CJD caused by a pathogenic PRNP mutation at codon 180. These findings show that the effects of the PRNP polymorphisms may be more complicated than previously thought. This review aims to summarize recent advances in our knowledge about the influence of the PRNP polymorphisms on the prion disease susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Asano M, Mohri S, Ironside JW, Ito M, Tamaoki N, Kitamoto T (2006) vCJD prion acquires altered virulence through trans-species infection. Biochem Biophys Res Commun 342:293–299

    Article  CAS  PubMed  Google Scholar 

  2. Biljan I, Giachin G, Ilc G, Zhukov I, Plavec J, Legname G (2012) Structural basis for the protective effect of the human prion protein carrying the dominant-negative E219 K polymorphism. Biochem J 446:243–251

    Article  CAS  PubMed  Google Scholar 

  3. Biljan I, Ilc G, Giachin G, Raspadori A, Zhukov I, Plavec J et al (2011) Toward the molecular basis of inherited prion diseases: NMR structure of the human prion protein with V210I mutation. J Mol Biol 412:660–673

    Article  CAS  PubMed  Google Scholar 

  4. Billette de Villemeur T, Gelot A, Deslys JP, Dormont D, Duyckaerts C, Jardin L et al (1994) Iatrogenic Creutzfeldt–Jakob disease in three growth hormone recipients: a neuropathological study. Neuropathol Appl Neurobiol 20:111–117

    Article  CAS  PubMed  Google Scholar 

  5. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V et al (2006) Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5:393–398

    Article  CAS  PubMed  Google Scholar 

  6. Bishop MT, Will RG, Manson JC (2010) Defining sporadic Creutzfeldt–Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 107:12005–12010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Brandel JP, Preece M, Brown P, Croes E, Laplanche JL, Agid Y et al (2003) Distribution of codon 129 genotype in human growth hormone-treated CJD patients in France and the UK. Lancet 362:128–130

    Article  CAS  PubMed  Google Scholar 

  8. Brown P, Brandel JP, Sato T, Nakamura Y, MacKenzie J, Will RG et al (2012) Iatrogenic Creutzfeldt–Jakob disease, final assessment. Emerg Infect Dis 18:901–907

    Article  PubMed Central  PubMed  Google Scholar 

  9. Capellari S, Strammiello R, Saverioni D, Kretzschmar H, Parchi P (2011) Genetic Creutzfeldt–Jakob disease and fatal familial insomnia: insights into phenotypic variability and disease pathogenesis. Acta Neuropathol 121:21–37

    Article  CAS  PubMed  Google Scholar 

  10. Cervenáková L, Goldfarb LG, Garruto R, Lee HS, Gajdusek DC, Brown P (1998) Phenotype–genotype studies in kuru: implications for new variant Creutzfeldt–Jakob disease. Proc Natl Acad Sci USA 95:13239–13241

    Article  PubMed Central  PubMed  Google Scholar 

  11. Chen SG, Parchi P, Brown P, Capellari S, Zou W, Cochran EJ et al (1997) Allelic origin of the abnormal prion protein isoform in familial prion diseases. Nat Med 3:1009–1015

    Article  CAS  PubMed  Google Scholar 

  12. Colby DW, Prusiner SB (2011) Prions. Cold Spring Harb Perspect. Biol 3:a006833

    Google Scholar 

  13. Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt–Jakob disease. Lancet 337:1141–1142

    Article  Google Scholar 

  14. Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685–690

    Article  CAS  PubMed  Google Scholar 

  15. Delisle MB, Fabre N, Rochiccioli P, Doerr-Schott J, Rumeau JL, Bes A (1993) Creutzfeldt–Jakob disease after treatment with human extracted growth hormone. A clinicopathological study. Rev Neurol (Paris) 149:524–527

    CAS  Google Scholar 

  16. DeMarco ML, Daggett V (2004) From conversion to aggregation: protofibril formation of the prion protein. Proc Natl Acad Sci USA 101:2293–2298

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Deslys JP, Marcé D, Dormont D (1994) Similar genetic susceptibility in iatrogenic and sporadic Creutzfeldt–Jakob disease. J Gen Virol 75:23–27

    Article  CAS  PubMed  Google Scholar 

  18. Diack AB, Head MW, McCutcheon S, Boyle A, Knight R, Ironside JW et al (2014) Variant CJD: 18 years of research and surveillance. Prion 8:286–295

    Article  CAS  PubMed  Google Scholar 

  19. Diack AB, Ritchie DL, Peden AH, Brown D, Boyle A, Morabito L et al (2014) Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerg Infect Dis 20:1969–1979

    Article  PubMed Central  PubMed  Google Scholar 

  20. Doh-ura K, Kitamoto T, Sakaki Y, Tateishi J (1991) CJD discrepancy. Nature 353:801–802

    Article  CAS  PubMed  Google Scholar 

  21. Gabizon R, Telling G, Meiner Z, Halimi M, Kahana I, Prusiner SB (1996) Insoluble wild-type and protease-resistant mutant prion protein in brains of patients with inherited prion disease. Nat Med 2:59–64

    Article  CAS  PubMed  Google Scholar 

  22. Gambetti P, Puoti G, Zou WQ (2011) Variably protease-sensitive prionopathy: a novel disease of the prion protein. J Mol Neurosci 45:422–424

    Article  CAS  PubMed  Google Scholar 

  23. Gill ON, Spencer Y, Richard-Loendt A, Kelly C, Dabaghian R, Boyes L et al (2013) Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 347:f5675

    Article  PubMed Central  PubMed  Google Scholar 

  24. Govaerts C, Wille H, Prusiner SB, Cohen FE (2004) Evidence for assembly of prions with left-handed beta-helices into trimers. Proc Natl Acad Sci USA 101:8342–8347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Hainfellner JA, Parchi P, Kitamoto T, Jarius C, Gambetti P, Budka H (1999) A novel phenotype in familial Creutzfeldt–Jakob disease: prion protein gene E200 K mutation coupled with valine at codon 129 and type 2 protease-resistant prion protein. Ann Neurol 45:812–816

    Article  CAS  PubMed  Google Scholar 

  26. Hamaguchi T, Sakai K, Noguchi-Shinohara M, Nozaki I, Takumi I, Sanjo N et al (2013) Insight into the frequent occurrence of dura mater graft-associated Creutzfeldt–Jakob disease in Japan. J Neurol Neurosurg Psychiatry 84:1171–1175

    Article  PubMed  Google Scholar 

  27. Health Protection Agency (2007) Fourth case of transfusion-associated variant-CJD infection. Health Protection Report 1

  28. Heinemann U, Krasnianski A, Meissner B, Varges D, Kallenberg K, Schulz-Schaeffer WJ et al (2007) Creutzfeldt–Jakob disease in Germany: a prospective 12-year surveillance. Brain 130:1350–1359

    Article  CAS  PubMed  Google Scholar 

  29. Hizume M, Kobayashi A, Teruya K, Ohashi H, Ironside JW, Mohri S et al (2009) Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt–Jakob disease infection. J Biol Chem 284:3603–3609

    Article  CAS  PubMed  Google Scholar 

  30. Hosszu LL, Jackson GS, Trevitt CR, Jones S, Batchelor M, Bhelt D et al (2004) The residue 129 polymorphism in human prion protein does not confer susceptibility to Creutzfeldt–Jakob disease by altering the structure or global stability of PrPC. J Biol Chem 279:28515–28521

    Article  CAS  PubMed  Google Scholar 

  31. Ironside JW (2012) Variant Creutzfeldt–Jakob disease: an update. Folia Neuropathol 50:50–56

    CAS  PubMed  Google Scholar 

  32. Kaneko K, Zulianello L, Scott M, Cooper CM, Wallace AC, James TL et al (1997) Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc Natl Acad Sci USA 94:10069–10074

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Kitamoto T, Tateishi J (1994) Human prion diseases with variant prion protein. Philos Trans R Soc Lond B Biol Sci 343:391–398

    Article  CAS  PubMed  Google Scholar 

  34. Kobayashi A, Asano M, Mohri S, Kitamoto T (2007) Cross-sequence transmission of sporadic Creutzfeldt–Jakob disease creates a new prion strain. J Biol Chem 282:30022–30028

    Article  CAS  PubMed  Google Scholar 

  35. Kobayashi A, Asano M, Mohri S, Kitamoto T (2009) A traceback phenomenon can reveal the origin of prion infection. Neuropathology 29:619–624

    Article  PubMed  Google Scholar 

  36. Kobayashi A, Hizume M, Teruya K, Mohri S, Kitamoto T (2009) Heterozygous inhibition in prion infection: the stone fence model. Prion 3:27–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Kobayashi A, Iwasaki Y, Otsuka H, Yamada M, Yoshida M, Matsuura Y et al (2013) Deciphering the Pathogenesis of Sporadic Creutzfeldt–Jakob Disease with Codon 129 M/V and Type 2 Abnormal Prion Protein. Acta Neuropathol Commun 1:74

    Article  PubMed Central  PubMed  Google Scholar 

  38. Kobayashi A, Matsuura Y, Iwaki T, Iwasaki Y, Yoshida M, Takahashi H et al (2015) Sporadic Creutzfeldt–Jakob disease MM1 + 2C and MM1 are identical in transmission properties. Brain Pathol. doi:10.1111/bpa.12264

    PubMed  Google Scholar 

  39. Kobayashi A, Matsuura Y, Mohri S, Kitamoto T (2014) Distinct origins of dura mater graft-associated Creutzfeldt–Jakob disease: past and future problems. Acta Neuropathol Commun 2:32

    Article  PubMed Central  PubMed  Google Scholar 

  40. Kobayashi A, Parchi P, Yamada M, Brown P, Saverioni D, Matsuura Y et al (2015) Transmission properties of atypical Creutzfeldt–Jakob disease: a clue to disease etiology? J Virol 89:3939–3946

    Article  CAS  PubMed  Google Scholar 

  41. Kobayashi A, Sakuma N, Matsuura Y, Mohri S, Aguzzi A, Kitamoto T (2010) Experimental verification of a traceback phenomenon in prion infection. J Virol 84:3230–3238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Korth C, Kaneko K, Groth D, Heye N, Telling G, Mastrianni J (2003) Abbreviated incubation times for human prions in mice expressing a chimeric mouse–human prion protein transgene. Proc Natl Acad Sci USA 100:4784–4789

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Kovács GG, Puopolo M, Ladogana A, Pocchiari M, Budka H, van Duijn C et al (2005) Genetic prion disease: the EUROCJD experience. Hum Genet 118:166–174

    Article  PubMed  Google Scholar 

  44. Langedijk JP, Fuentes G, Boshuizen R, Bonvin AM (2006) Two-rung model of a left-handed beta-helix for prions explains species barrier and strain variation in transmissible spongiform encephalopathies. J Mol Biol 360:907–920

    Article  CAS  PubMed  Google Scholar 

  45. Laplanche JL, Delasnerie-Lauprêtre N, Brandel JP, Chatelain J, Beaudry P, Alpérovitch A et al (1994) Molecular genetics of prion diseases in France. French Research Group on Epidemiology of Human Spongiform Encephalopathies. Neurology 44:2347–2351

    Article  CAS  PubMed  Google Scholar 

  46. Lee HS, Brown P, Cervenáková L, Garruto RM, Alpers MP, Gajdusek DC et al (2001) Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype. J Infect Dis 183:192–196

    Article  CAS  PubMed  Google Scholar 

  47. Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J et al (2004) Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. Lancet 363:417–421

    Article  CAS  PubMed  Google Scholar 

  48. Lukic A, Beck J, Joiner S, Fearnley J, Sturman S, Brandner S et al (2010) Heterozygosity at polymorphic codon 219 in variant Creutzfeldt–Jakob disease. Arch Neurol 67:1021–1023

    Article  PubMed  Google Scholar 

  49. López Garcia F, Zahn R, Riek R, Wüthrich K (2000) NMR structure of the bovine prion protein. Proc Natl Acad Sci USA 97:8334–8339

    Article  PubMed Central  PubMed  Google Scholar 

  50. Mead S, Stumpf MP, Whitfield J, Beck JA, Poulter M, Campbell T et al (2003) Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300:640–643

    Article  CAS  PubMed  Google Scholar 

  51. Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T et al (2009) A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med 361:2056–2065

    Article  CAS  PubMed  Google Scholar 

  52. Moda F, Suardi S, Di Fede G, Indaco A, Limido L, Vimercati C et al (2012) MM2-thalamic Creutzfeldt–Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain. Brain Pathol 22:662–669

    Article  CAS  PubMed  Google Scholar 

  53. Mitrová E, Belay G (2002) Creutzfeldt–Jakob disease in health professionals in Slovakia. Acta Virol 46:31–39

    PubMed  Google Scholar 

  54. Noguchi-Shinohara M, Hamaguchi T, Kitamoto T, Sato T, Nakamura Y, Mizusawa H et al (2007) Clinical features and diagnosis of dura mater graft associated Creutzfeldt–Jakob disease. Neurology 69:360–367

    Article  CAS  PubMed  Google Scholar 

  55. Notari S, Capellari S, Giese A, Westner I, Baruzzi A, Ghetti B et al (2004) Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD. J Biol Chem 279:16797–16804

    Article  CAS  PubMed  Google Scholar 

  56. Notari S, Xiao X, Espinosa JC, Cohen Y, Qing L, Aguilar-Calvo P et al (2014) Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect Dis 20:2006–2014

    Article  PubMed Central  PubMed  Google Scholar 

  57. Nozaki I, Hamaguchi T, Sanjo N, Noguchi-Shinohara M, Sakai K, Nakamura Y et al (2010) Prospective 10-year surveillance of human prion diseases in Japan. Brain 133:3043–3057

    Article  PubMed  Google Scholar 

  58. Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352:340–342

    Article  CAS  PubMed  Google Scholar 

  59. Parchi P, Capellari S, Chen SG, Petersen RB, Gambetti P, Kopp N et al (1997) Typing prion isoforms. Nature 386:232–234

    Article  CAS  PubMed  Google Scholar 

  60. Parchi P, Cescatti M, Notari S, Schulz-Schaeffer WJ, Capellari S, Giese A et al (2010) Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease. Brain 133:3030–3042

    Article  PubMed Central  PubMed  Google Scholar 

  61. Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O et al (1999) Classification of sporadic Creutzfeldt–Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233

    Article  CAS  PubMed  Google Scholar 

  62. Parchi P, Petersen RB, Chen SG, Autilio-Gambetti L, Capellari S, Monari L et al (1998) Molecular pathology of fatal familial insomnia. Brain Pathol 8:531–537

    PubMed  Google Scholar 

  63. Parchi P, Zou W, Wang W, Brown P, Capellari S, Ghetti B et al (2000) Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci USA 97:10168–10172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Peden A, McCardle L, Head MW, Love S, Ward HJ, Cousens SN et al (2010) Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 16:296–304

    Article  CAS  PubMed  Google Scholar 

  65. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364:527–529

    Article  PubMed  Google Scholar 

  66. Petraroli R, Pocchiari M (1996) Codon 219 polymorphism of PRNP in healthy Caucasians and Creutzfeldt–Jakob disease patients. Am J Hum Genet 58:888–889

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Prusiner SB, Scott MR, DeArmond SJ, Cohen FE (1998) Prion protein biology. Cell 93:337–348

    Article  CAS  PubMed  Google Scholar 

  68. Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P et al (2012) Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol 11:618–628

    Article  CAS  PubMed  Google Scholar 

  69. Qina T, Sanjo N, Hizume M, Higuma M, Tomita M, Atarashi R et al (2014) Clinical features of genetic Creutzfeldt–Jakob disease with V180I mutation in the prion protein gene. BMJ Open 4:e004968

    Article  PubMed Central  PubMed  Google Scholar 

  70. Salvatore M, Genuardi M, Petraroli R, Masullo C, D’Alessandro M, Pocchiari M (1994) Polymorphisms of the prion protein gene in Italian patients with Creutzfeldt–Jakob disease. Hum Genet 94:375–379

    Article  CAS  PubMed  Google Scholar 

  71. Shibuya S, Higuchi J, Shin RW, Tateishi J, Kitamoto T (1998) Protective prion protein polymorphisms against sporadic Creutzfeldt–Jakob disease. Lancet 351:419

    Article  CAS  PubMed  Google Scholar 

  72. Shirai T, Saito M, Kobayashi A, Asano M, Hizume M, Ikeda S et al (2014) Evaluating prion models based on comprehensive mutation data of mouse PrP. Structure 22:560–571

    Article  CAS  PubMed  Google Scholar 

  73. Silvestrini MC, Cardone F, Maras B, Pucci P, Barra D, Brunori M et al (1997) Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt–Jakob disease patients. Nat Med 3:521–525

    Article  CAS  PubMed  Google Scholar 

  74. Soldevila M, Calafell F, Andrés AM, Yagüe J, Helgason A, Stefánsson K et al (2003) Prion susceptibility and protective alleles exhibit marked geographic differences. Hum Mutat 22:104–105

    Article  PubMed  Google Scholar 

  75. Takeuchi A, Kobayashi A, Ironside JW, Mohri S, Kitamoto T (2013) Characterization of variant Creutzfeldt–Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes. J Biol Chem 288:21659–21666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Wadsworth JD, Joiner S, Linehan JM, Asante EA, Brandner S, Collinge J (2008) Review. The origin of the prion agent of kuru: molecular and biological strain typing. Philos Trans R Soc Lond B Biol Sci 363:3747–3753

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Wadsworth JD, Joiner S, Linehan JM, Cooper S, Powell C, Mallinson G et al (2006) Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion protein. Brain 129:1557–1569

    Article  PubMed  Google Scholar 

  78. Wadsworth JD, Joiner S, Linehan JM, Desbruslais M, Fox K, Cooper S et al (2008) Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proc Natl Acad Sci USA 105:3885–3890

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Watts JC, Giles K, Stöhr J, Oehler A, Bhardwaj S, Grillo SK et al (2012) Spontaneous generation of rapidly transmissible prions in transgenic mice expressing wild-type bank vole prion protein. Proc Natl Acad Sci USA 109:3498–3503

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A et al (1996) A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347:921–925

    Article  CAS  PubMed  Google Scholar 

  81. Windl O, Dempster M, Estibeiro JP, Lathe R, de Silva R, Esmonde T et al (1996) Genetic basis of Creutzfeldt–Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 98:259–264

    Article  CAS  PubMed  Google Scholar 

  82. Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S et al (2006) Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt–Jakob disease associated with blood transfusion: a case report. Lancet 368:2061–2067

    Article  PubMed  Google Scholar 

  83. Xiao X, Yuan J, Haïk S, Cali I, Zhan Y, Moudjou M et al (2013) Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS One 8:e58786

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Yamada M, Itoh Y, Inaba A, Wada Y, Takashima M, Satoh S et al (1999) An inherited prion disease with a PrP P105L mutation: clinicopathologic and PrP heterogeneity. Neurology 53:181–188

    Article  CAS  PubMed  Google Scholar 

  85. Yamada M, Noguchi-Shinohara M, Hamaguchi T, Nozaki I, Kitamoto T, Sato T et al (2009) Dura mater graft-associated Creutzfeldt–Jakob disease in Japan: clinicopathological and molecular characterization of the two distinct subtypes. Neuropathology 29:609–618

    Article  PubMed  Google Scholar 

  86. Young K, Clark HB, Piccardo P, Dlouhy SR, Ghetti B (1997) Gerstmann–Sträussler–Scheinker disease with the PRNP P102L mutation and valine at codon 129. Brain Res Mol Brain Res 44:147–150

    Article  CAS  PubMed  Google Scholar 

  87. Zou WQ, Puoti G, Xiao X, Yuan J, Qing L, Cali I et al (2010) Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein. Ann Neurol 68:162–172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank members of the Creutzfeldt–Jakob Disease Surveillance Committee in Japan, Creutzfeldt–Jakob disease specialists in the prefectures, and Creutzfeldt–Jakob disease patients and families for providing important clinical information. We thank Y. Ishikawa, H. Kudo, M. Yamamoto, and A. Yamazaki for their excellent technical assistance, and B. Bell for critical review of the manuscript. This study was supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare of Japan (A.K., Y.N., M.Y., H.M., S.M. and T.K.), Grants-in-Aid for Scientific Research from JSPS (A.K. and T.K.), the Platform for Drug Design, Informatics, and Structural Lifescience (PDIS) (T.S.), a grant from MEXT for the Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University (T.K.), and a Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (T.K.).

Conflict of interest

The authors declare that they have no conflicting interest.

Author information

Authors and Affiliations

  1. Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Atsushi Kobayashi, Shirou Mohri & Tetsuyuki Kitamoto

  2. Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 13 Taishogun, Nishitakatsukasa-cho, Kita-ku, Kyoto, 603-8334, Japan

    Kenta Teruya

  3. Influenza and Prion Disease Research Center, National Institute of Animal Health, Tsukuba, 305-0856, Japan

    Yuichi Matsuura

  4. Department of Computer Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, 526-0829, Japan

    Tsuyoshi Shirai

  5. Department of Public Health, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan

    Yoshikazu Nakamura

  6. Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8640, Japan

    Masahito Yamada

  7. National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi-machi, Kodaira, 187-8511, Japan

    Hidehiro Mizusawa

  8. Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan

    Atsushi Kobayashi

Authors
  1. Atsushi Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenta Teruya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuichi Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsuyoshi Shirai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshikazu Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masahito Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hidehiro Mizusawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shirou Mohri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tetsuyuki Kitamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuyuki Kitamoto.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kobayashi, A., Teruya, K., Matsuura, Y. et al. The influence of PRNP polymorphisms on human prion disease susceptibility: an update. Acta Neuropathol 130, 159–170 (2015). https://doi.org/10.1007/s00401-015-1447-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-015-1447-7

Keywords

Search

Navigation