Citation

Cracco L, Appleby BS, Gambetti P. Handb. Clin. Neurol. 2018; 153: 271-299.

Affiliation

Department of Pathology, Case Western Reserve University, Cleveland, OH, United States. Electronic address: pxg13@case.edu.

Copyright

(Copyright © 2018, Elsevier Publishing)

DOI

10.1016/B978-0-444-63945-5.00015-5

PMID

29887141

Abstract

Fatal familial insomnia (FFI) and sporadic fatal insomnia (sFI), or thalamic form of sporadic Creutzfeldt-Jakob disease MM2 (sCJDMM2T), are prion diseases originally named and characterized in 1992 and 1999, respectively. FFI is genetically determined and linked to a D178N mutation coupled with the M129 genotype in the prion protein gene (PRNP) at chromosome 20. sFI is a phenocopy of FFI and likely its sporadic form. Both diseases are primarily characterized by progressive sleep impairment, disturbances of autonomic nervous system, and motor signs associated with severe loss of nerve cells in medial thalamic nuclei. Both diseases harbor an abnormal disease-associated prion protein isoform, resistant to proteases with relative mass of 19 kDa identified as resPrP^TSE type 2. To date at least 70 kindreds affected by FFI with 198 members and 18 unrelated carriers along with 25 typical cases of sFI have been published. The D178N-129M mutation is thought to cause FFI by destabilizing the mutated prion protein and facilitating its conversion to PrP^TSE. The thalamus is the brain region first affected. A similar mechanism triggered spontaneously may underlie sFI.

Copyright © 2018 Elsevier B.V. All rights reserved.

Language: en

Keywords

D178N; PET; polymorphism; polysomnography; prion; propagation; sCJDMM2; spindle; strain; thalamic