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Hereditary Human Prion Diseases: an Update

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Abstract

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.

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Abbreviations

FFI:

Fatal familial insomnia

PRNP :

Prion protein gene

PrPSc :

Scrapie prion protein

CJD:

Creutzfeldt-Jakob disease

gCJD:

Genetic CJD

sCJD:

Sporadic CJD

OPRI:

Octa-peptide repeat insertion

GSS:

Gerstmann-Sträussler-Scheinker syndrome

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Authors and Affiliations

  1. Department of Neurology, University Medical Center Göttingen and the German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany

    Matthias Schmitz, Kathrin Dittmar, Franc Llorens & Inga Zerr

  2. Department of Neuropathology, Georg-August University, Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Matthias Schmitz & Walter J. Schulz-Schaeffer

  3. Neurological Tissue Bank, Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain

    Ellen Gelpi

  4. Institute of Neuropathology, Bellvitge University Hospital, CIBERNED, Hospitalet de Llobregat, University of Barcelona, Barcelona, Spain

    Isidre Ferrer

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  1. Matthias Schmitz
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Schmitz, M., Dittmar, K., Llorens, F. et al. Hereditary Human Prion Diseases: an Update. Mol Neurobiol 54, 4138–4149 (2017). https://doi.org/10.1007/s12035-016-9918-y

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