Disease relevance of Insomnia, Fatal Familial

• An aberrant form of PrPc that is partially resistant to proteases, PrPres, is a hallmark of prion diseases, which in humans include Cruetzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia [1].
• Discovery of mutations in the PrP gene from humans with Gerstmann-Sträussler-Scheinker disease (GSS), familial Creutzfeldt-Jakob disease and fatal familial insomnia established that prion diseases are unique among human illnesses--they are both genetic and infectious [2].
• Humans are also susceptible to several prion diseases: Creutzfeld-Jacob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome (GSS), Fatal Familial Insomnia (FFI), Kuru and Alpers Syndrome [3].
• Prion diseases include kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia of humans as well as scrapie and bovine spongiform encephalopathy of animals [4].

Psychiatry related information on Insomnia, Fatal Familial

• Protease-resistant PrP was found in both patients with fatal familial insomnia, but the size and number of protease-resistant fragments differed from those in Creutzfeldt-Jakob disease [5].
• Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease [6].

High impact information on Insomnia, Fatal Familial

• To our knowledge, this is the first null mutation that has been shown to affect sleep regulation and our results indicate that at least one of the inherited prion diseases, fatal familial insomnia, where there is a profound alteration in sleep and the daily rhythms of many hormones, may be related to the normal function of the prion protein [7].
• As a group, familial cases had lower amyloid protein concentrations than either sporadic or iatrogenic cases, and fatal familial insomnia patients had the lowest concentrations found in any form of disease [8].
• Protease-resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia [9].
• In 1986, a heritable total insomnia was described and termed fatal familial insomnia; since then, the pathology of this disease has been shown to involve an accumulation of prion particles in the brains of affected patients [10].
• [18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions [11].

Chemical compound and disease context of Insomnia, Fatal Familial

• Fatal familial insomnia (FFI) has been exclusively associated with a pathogenic mutation at codon 178 in the PRNP gene coupled with methionine (Met) at codon 129 [12].
• We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene [11].
• Selective thalamic degenerations share clinical and pathologic features with fatal familial insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the prion protein (PrP) gene that causes the substitution of asparagine for aspartic acid (178Asn mutation) [6].
• Combined quinacrine and chlorpromazine therapy in fatal familial insomnia [13].
• The objective of this paper was to report on 2 fatal familial insomnia patients whose overall condition worsened despite quinacrine and chlorpromazine treatment [13].

Biological context of Insomnia, Fatal Familial

• Transgenic (Tg) mice expressing a chimeric human-mouse PrP transgene were inoculated with brain extracts from three fCJD(V210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics [14].
• All inherited forms of human TSEs, i.e., familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia, segregate with specific point mutations or insertions in the gene coding for human PrP [15].

Gene context of Insomnia, Fatal Familial

• The coding region of the PrP gene was amplified and sequenced in the samples from the two patients with fatal familial insomnia [5].
• Dissociated 24-hour patterns of somatotropin and prolactin in fatal familial insomnia [16].
• Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia [17].
• Fatal familial insomnia is another inherited disorder due to a mutation at codon 178 of the PRP gene associated with methionine on codon 129 of the mutant allele [18].

Analytical, diagnostic and therapeutic context of Insomnia, Fatal Familial

• METHODS: Seventeen healthy individuals belonging to a single fatal familial insomnia pedigree, 8 carriers and 9 non-carriers of the PRNP codon 178 mutation, underwent polysomnography and spectral electroencephalographic (EEG) analysis [19].

References