Skip to main content

Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease


Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50–59 year group. Gerstmann–Sträussler–Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Availability of Data and Materials

Data are available on reasonable request. All anonymized data from this study will be shared on request from any qualified investigator. Data reuse is permitted only for academic purposes.


  1. 1.

    Gill AC, Castle AR. The cellular and pathologic prion protein. Handb Clin Neurol 2018, 153: 21–44.

    Article  Google Scholar 

  2. 2.

    Chen C, Dong XP. Epidemiological characteristics of human prion diseases. Infect Dis Poverty 2016, 5: 47.

    Article  Google Scholar 

  3. 3.

    Ironside JW, Ritchie DL, Head MW. Prion diseases. Handb Clin Neurol 2017, 145: 393–403.

    Article  Google Scholar 

  4. 4.

    Jeong BH, Kim YS. Genetic studies in human prion diseases. J Korean Med Sci 2014, 29: 623–632.

    CAS  Article  Google Scholar 

  5. 5.

    Kim MO, Takada LT, Wong K, Forner SA, Geschwind MD. Genetic PrP prion diseases. Cold Spring Harb Perspect Biol 2018, 10.

  6. 6.

    Kovács GG, Puopolo M, Ladogana A, Pocchiari M, Budka H, van Duijn C. Genetic prion disease: The EUROCJD experience. Hum Genet 2005, 118: 166–174.

    Article  Google Scholar 

  7. 7.

    Ladogana A, Puopolo M, Poleggi A, Almonti S, Mellina V, Equestre M, et al. High incidence of genetic human transmissible spongiform encephalopathies in Italy. Neurology 2005, 64: 1592–1597.

    CAS  Article  Google Scholar 

  8. 8.

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

    CAS  Article  Google Scholar 

  9. 9.

    Mouillet-Richard S, Teil C, Lenne M, Hugon S, Taleb O, Laplanche JL. Mutation at Codon 210 (V210I) of the prion protein gene in a North African patient with Creutzfeldt-Jakob disease. J Neurol Sci 1999, 168: 141–144.

    CAS  Article  Google Scholar 

  10. 10.

    Huang N, Marie SK, Kok F, Nitrini R. Familial Creutzfeldt-Jakob disease associated with a point mutation at Codon 210 of the prion protein gene. Arq Neuropsiquiatr 2001, 59: 932–935.

    CAS  Article  Google Scholar 

  11. 11.

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

    Article  Google Scholar 

  12. 12.

    Shi Q, Zhou W, Chen C, Zhang BY, Xiao K, Zhang XC, et al. The features of genetic prion diseases based on Chinese surveillance program. PLoS One 2015, 10: e0139552.

    Article  Google Scholar 

  13. 13.

    Shi Q, Zhou W, Chen C, Zhang BY, Xiao K, Zhang XC, et al. The features of genetic prion diseases based on Chinese surveillance program. PLoS One 2015, 10: e0139552.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Shi Q, Gao C, Zhou W, Zhang BY, Chen JM, Tian C, et al. Surveillance for creutzfeldt-Jakob disease in China from 2006 to 2007. BMC Public Heal 2008, 8: 1–6.

    Article  Google Scholar 

  15. 15.

    Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 2009, 132: 2659–2668.

    CAS  Article  Google Scholar 

  16. 16.

    Chen C, Hu C, Shi Q, Zhou W, Xiao K, Wang Y, et al. Profiles of 14-3-3 and total tau in CSF samples of Chinese patients of different genetic prion diseases. Front Neurosci 2019, 13: 934.

    Article  Google Scholar 

  17. 17.

    Xiao K, Shi Q, Zhou W, Zhang BY, Wang Y, Chen C, et al. T188K-familial creutzfeldt-Jacob disease, predominant among Chinese, has a reactive pattern in CSF RT-QuIC different from D178N-fatal familial insomnia and E200K-familial CJD. Neurosci Bull 2019, 35: 519–521.

    CAS  Article  Google Scholar 

  18. 18.

    Shi Q, Xiao K, Zhou W, Wang J, Dong XP. Fatal familial insomnia: Insight of the most common genetic prion disease in China based on the analysis of 40 patients. 2018

  19. 19.

    Wang J, Xiao K, Zhou W, Shi Q, Dong XP. Analysis of 12 Chinese patients with proline-to-leucine mutation at Codon 102-associated gerstmann-sträussler-scheinker disease. J Clin Neurol 2019, 15: 184–190.

    Article  Google Scholar 

  20. 20.

    Shi XH, Han J, Zhang J, Shi Q, Chen JM, Xia SL, et al. Clinical, histopathological and genetic studies in a family with fatal familial insomnia. Infect Genet Evol 2010, 10: 292–297.

    CAS  Article  Google Scholar 

  21. 21.

    Xie WL, Shi Q, Xia SL, Zhang BY, Gong HS, Wang SB, et al. Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia. Int J Mol Med 2013, 31: 81–90.

    CAS  Article  Google Scholar 

  22. 22.

    Kovacs GG, Seguin J, Quadrio I, Höftberger R, Kapás I, Streichenberger N, et al. Genetic Creutzfeldt-Jakob disease associated with the E200K mutation: Characterization of a complex proteinopathy. Acta Neuropathol 2011, 121: 39–57.

    CAS  Article  Google Scholar 

  23. 23.

    Mitrová E, Belay G. Creutzfeldt-Jakob disease with E200K mutation in Slovakia: Characterization and development. Acta Virol 2002, 46: 31–39.

    PubMed  Google Scholar 

  24. 24.

    Minikel EV, Vallabh SM, Orseth MC, Brandel JP, Haïk S, Laplanche JL, et al. Age at onset in genetic prion disease and the design of preventive clinical trials. Neurology 2019, 93: e125–e134.

    CAS  Article  Google Scholar 

  25. 25.

    Gao LP, Shi Q, Xiao K, Wang J, Zhou W, Chen C, et al. The genetic Creutzfeldt-Jakob disease with E200K mutation: Analysis of clinical, genetic and laboratory features of 30 Chinese patients. Sci Rep 1836, 2019: 9.

    Google Scholar 

  26. 26.

    Shi Q, Zhou W, Chen C, Xiao K, Wang Y, Gao C, et al. Rare genetic Creutzfeldt-Jakob disease with T188K mutation: Analysis of clinical, genetic and laboratory features of30 Chinese patients. J Neurol Neurosurg Psychiatry 2017, 88: 889–890.

    Article  Google Scholar 

  27. 27.

    Chen C, Wang JC, Shi Q, Zhou W, Zhang XM, Zhang J, et al. Analyses of the survival time and the influencing factors of Chinese patients with prion diseases based on the surveillance data from 2008–2011. PLoS One 2013, 8: e62553.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Shi Q, Zhang BY, Gao C, Han J, Wang GR, Chen C, et al. The diversities of PrP(Sc) distributions and pathologic changes in various brain regions from a Chinese patient with G114V genetic CJD. Neuropathology 2012, 32: 51–59.

    Article  Google Scholar 

  29. 29.

    Wang XF, Guo YJ, Zhang BY, Zhao WQ, Gao JM, Wan YZ, et al. Creutzfeldt-Jakob disease in a Chinese patient with a novel seven extra-repeat insertion in PRNP. J Neurol Neurosurg Psychiatry 2007, 78: 201–203.

    CAS  Article  Google Scholar 

  30. 30.

    Guo YJ, Wang XF, Han J, Zhang BY, Zhao WQ, Shi Q, et al. A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: Molecular characteristics and clinical features. Am J Med Sci 2008, 336: 519–523.

    Article  Google Scholar 

  31. 31.

    Minikel EV, Vallabh SM, Lek M, Estrada K, Samocha KE, Sathirapongsasuti JF, et al. Quantifying prion disease penetrance using large population control cohorts. Sci Transl Med 2016, 8: 322ra9.

    Article  Google Scholar 

  32. 32.

    Takada LT, Kim MO, Cleveland RW, Wong K, Forner SA, Gala II, et al. Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature. Am J Med Genet B Neuropsychiatr Genet 2017, 174: 36–69.

    Article  Google Scholar 

  33. 33.

    Higuma M, Sanjo N, Satoh K, Shiga Y, Sakai, Nozaki I, et al. Relationships between clinicopathological features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases. PLoS One 2013, 8: e60003. DOI:

  34. 34.

    Finckh U, Müller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, et al. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet 2000, 66: 110–117.

    CAS  Article  Google Scholar 

  35. 35.

    Zhang HL, Wang MB, Wu LM, Zhang HN, Jin T, Wu J, et al. Novel prion protein gene mutation at Codon 196 (E196A) in a septuagenarian with Creutzfeldt-Jakob disease. J Clin Neurosci 2014, 21: 175–178.

    Article  Google Scholar 

  36. 36.

    Shi Q, Zhou W, Chen C, Zhang BY, Xiao K, Wang Y, et al. Rare E196A mutation in PRNP gene of 3 Chinese patients with Creutzfeldt-Jacob disease. Prion 2016, 10: 331–337.

    CAS  Article  Google Scholar 

Download references


This work was supported by the National Natural Science Foundation of China (81630062) and the State Key Laboratory for Infectious Disease Prevention and Control, CDC, China (2019SKLID501, 2019SKLID603, and 2019SKLID307).

Author information



Corresponding authors

Correspondence to Qi Shi or Xiao-Ping Dong.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Patient Consent

Use of patients’ information stored by the China National Surveillance for CJD (CNS-CJD) was approved by the Research Ethics Committee of the National Institute for Viral Disease Control and Prevention, China CDC. Written informed consent for each case was given mostly by a member of the patient’s family according to the requirements of CJD surveillance.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shi, Q., Chen, C., Xiao, K. et al. Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease. Neurosci. Bull. (2021).

Download citation


  • Genetic prion disease
  • Mutation
  • Surveillance
  • Creutzfeldt–Jakob disease
  • Gerstmann–Sträussler–Scheinker syndrome
  • Fatal familial insomnia