Fatal Familial Insomnia, a Prion Disease with a Mutation at Codon 178 of the Prion Protein Gene

Abstract

Fatal familial insomnia is a prion disease with a mutation in codon 178 of the PrP gene, but the disease phenotype seems to differ from that of previously described kindreds with the same point mutation.

Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases

“…FFI is associated with the PRNP D178N/M129 haplotype; it is characterized clinically by profound sleep alterations and autonomic dysfunction, neuropathologically by severe degeneration of the anterior ventral and mediodorsal nuclei of the thalamus. 5 The disease is devastating usually leading to death within 2 y from onset, and no treatment is available. We have taken advantage of the unique opportunity to collaborate with a group of subjects belonging to a large Italian FFI kindred 6 organized in association, to design a clinical trial to evaluate the efficacy of a preventive drug treatment.…”

A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy

“…Dysautonomia has been reported in the rapidly progressive fatal familial insomnia, 23 which is classically caused by a mutation at codon 178 24 in association with methionine at polymorphic residue 129. However, peripheral neuropathy is not a feature of fatal familial insomnia.…”

An in vivo 11C‐PK PET study of microglia activation in Fatal Familial Insomnia

“…FFI is a rare disease4 linked to a missense mutation in the prion protein gene ( PRNP ) at codon‐178, with aspartate‐asparagine replacement (Asp→Asn) (D178N mutation),5, 6 which has a high, almost complete, penetrance 5, 6, 7. The D178N mutation can trigger different clinico‐pathological syndromes, either thalamic‐dominant FFI or CJD, depending on a methionine‐valine polymorphism at PRNP codon‐129 8, 9, 10.…”