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Fatal Familial Insomnia: Clinical Aspects and Molecular Alterations

  • Franc Llorens
  • Juan-José Zarranz
  • Andre Fischer
  • Inga Zerr
  • Isidro Ferrer
Sleep (M Thorpy and M Billiard, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Sleep

Abstract

Purpose of Review

Fatal familiar insomnia (FFI) is an autosomal dominant inherited prion disease caused by D178N mutation in the prion protein gene (PRNP D178N) accompanied by the presence of a methionine at the codon 129 polymorphic site on the mutated allele. FFI is characterized by severe sleep disorder, dysautonomia, motor signs and abnormal behaviour together with primary atrophy of selected thalamic nuclei and inferior olives, and expansion to other brain regions with disease progression. This article reviews recent research on the clinical and molecular aspects of the disease.

Recent Findings

New clinical and biomarker tools have been implemented in order to assist in the diagnosis of the disease. In addition, the generation of mouse models, the availability of ‘omics’ data in brain tissue and the use of new seeding techniques shed light on the molecular events in FFI pathogenesis. Biochemical studies in human samples also reveal that neuropathological alterations in vulnerable brain regions underlie severe impairment in key cellular processes such as mitochondrial and protein synthesis machinery.

Summary

Although the development of a therapy is still a major challenge, recent findings represent a step toward understanding of the clinical and molecular aspects of FFI.

Keywords

Prion protein Hereditary prion disease Fatal familial insomnia Neurodegenerative diseases Thalamus 

Notes

Acknowledgements

This study was supported by the EU joint programme-Neurodegenerative Disease Research (JPND-DEMTEST: biomarker based diagnosis of rapidly progressive dementias-optimization of diagnostic protocols, 01ED1201A) and the Robert Koch Institute thought (NRZ 1369-341) to IZ, by German Center for Neurodegenerative Diseases (DZNE) funds to AF, and by the Red Nacional de Priones (AGL2015-71764-REDT- MINECO) to FL, IZ and IF. We wish to thank T. Yohannan for editorial assistance.

Compliance with Ethical Standards

Conflict of Interest

Franc Llorens, Juan-José Zarranz, Andre Fischer, Inga Zerr, and Isidro Ferrer declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Neurology, Clinical Dementia Center, University Medical CenterGeorg-August UniversityGöttingenGermany
  2. 2.German Center for Neurodegenerative Diseases (DZNE)-site GöttingenGöttingenGermany
  3. 3.Neurology Department, University Hospital CrucesUniversity of the Basque CountryBilbaoSpain
  4. 4.Institute of NeuropathologyBellvitge University Hospital-IDIBELLBarcelonaSpain
  5. 5.University of BarcelonaL’Hospitalet de LlobregatBarcelonaSpain
  6. 6.CIBERNED (Network Centre for Biomedical Research of Neurodegenerative Diseases), Institute Carlos IIIMinistry of HealthMadridSpain

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