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

Abstract

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.

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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.

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Acknowledgements

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).

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Correspondence to Qi Shi or Xiao-Ping Dong.

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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.

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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). https://doi.org/10.1007/s12264-021-00764-y

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Keywords

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