Molecular Neurobiology

, Volume 54, Issue 6, pp 4138–4149 | Cite as

Hereditary Human Prion Diseases: an Update

  • Matthias SchmitzEmail author
  • Kathrin Dittmar
  • Franc Llorens
  • Ellen Gelpi
  • Isidre Ferrer
  • Walter J. Schulz-Schaeffer
  • Inga Zerr


Prion diseases in humans are neurodegenerative diseases which are caused by an accumulation of abnormal, misfolded cellular prion protein known as scrapie prion protein (PrPSc). Genetic, acquired, or spontaneous (sporadic) forms are known. Pathogenic mutations in the human prion protein gene (PRNP) have been identified in 10–15 % of CJD patients. These mutations may be single point mutations, STOP codon mutations, or insertions or deletions of octa-peptide repeats. Some non-coding mutations and new mutations in the PrP gene have been identified without clear evidence for their pathogenic significance. In the present review, we provide an updated overview of PRNP mutations, which have been documented in the literature until now, describe the change in the DNA, the family history, the pathogenicity, and the number of described cases, which has not been published in this complexity before. We also provide a description of each genetic prion disease type, present characteristic histopathological features, and the PrPSc isoform expression pattern of various familial/genetic prion diseases.


Hereditary human prion diseases Creutzfeldt-Jakob disease Fatal familial insomnia Gerstmann-Sträussler-Scheinker syndrome 



Fatal familial insomnia


Prion protein gene


Scrapie prion protein


Creutzfeldt-Jakob disease


Genetic CJD


Sporadic CJD


Octa-peptide repeat insertion


Gerstmann-Sträussler-Scheinker syndrome


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Matthias Schmitz
    • 1
    • 2
    Email author
  • Kathrin Dittmar
    • 1
  • Franc Llorens
    • 1
  • Ellen Gelpi
    • 3
  • Isidre Ferrer
    • 4
  • Walter J. Schulz-Schaeffer
    • 2
  • Inga Zerr
    • 1
  1. 1.Department of NeurologyUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases (DZNE)GöttingenGermany
  2. 2.Department of NeuropathologyGeorg-August UniversityGöttingenGermany
  3. 3.Neurological Tissue BankBiobanc-Hospital Clinic-IDIBAPSBarcelonaSpain
  4. 4.Institute of NeuropathologyBellvitge University Hospital, CIBERNED, Hospitalet de Llobregat, University of BarcelonaBarcelonaSpain

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