Phenotypic characteristics of familial Creutzfeldt‐Jakob disease assoicated with the codon 178^AsnPRNP mutation

Abstract

A group of 43 patients from seven families affected by Creutzfeldt-Jakob disease (CJD) with the codon 178Asn mutation of the PRNP amyloid precursor gene is compared to a group of 211 patients with the sporadic form of the disease. As a group, the patients with the codon 178Asn mutation had an earlier age at onset of illness (almost always presenting as an insidious loss of memory), a longer duration of illness, and an absence of periodic electroencephalographic activity. Transmission of disease to primates was accomplished using brain tissue homogenates from 6 of 10 patients, resulting in significantly shorter incubation periods than those due to sporadic CJD inocula. These findings are interpreted and discussed in terms of possible differences in the temporospatial evolution of damage to the brain, and of accelerated induction of polymerized amyloid protein by its mutationally altered template precursor.

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

“…One exception is CJD associated with point mutation at codon 178, where there is an earlier age at onset and a more protracted course. However, in this mutation, memory impairment is predominant as the initial symptom, and the clinical progression is similar to the sporadic forms of CJD, with a high frequency of cerebellar, myoclonus, extrapyramidal and pyramidal signs 6 .…”

“…Behavioral manifestation at the onset of the illness may also occur in other inherited prion diseases [6][7][8][9] . In CJD associated with other point mutations, the clinical features usually are extremely similar to the sporadic form of CJD, where, on average, symptoms begin at the age of 60 and death after 8 months of disease 1,2,6 .…”

“…In CJD associated with other point mutations, the clinical features usually are extremely similar to the sporadic form of CJD, where, on average, symptoms begin at the age of 60 and death after 8 months of disease 1,2,6 . One exception is CJD associated with point mutation at codon 178, where there is an earlier age at onset and a more protracted course.…”

Prion disease genetics

“…In 1992, Goldfarb et al 75 established a haplotypic relationship between codon 129 and 178, whereby the mutation on a 129M chromosome leads to FFI, and the mutation on a 129V chromosome leads to familial CJD. More recent experience questions such a tight association between haplotype and phenotype: some families do not obey the rule, 76 there are pedigrees that segregate both the FFI and CJD phenotype, 77 and it has become increasingly recognised that autonomic and sleep disturbances may accompany other PRNP mutations, sometimes overtly. 36 Cases reported to the CJD surveillance unit in Germany were less clinically distinct than the first reported FFI families in that none were clinically diagnosed as FFI due to an absence of obvious insomnia and no positive family history was obtained in 4/9.…”

Gold Nanoparticles as a Probe for Prion Determination via Resonance Light Scattering Method

“…7,11 Once such infection breaks out, it is hard to curtail and will spread rapidly. Diseases such as bovine spongiform encephalopathy, 12 scrapie 13,14 and Creutzfeld-Jakob disease, 15 variant CJD, 12,[15][16][17] fatal familial insomnia 9,15 and Gerstmann-Straussler-Scheinker syndrome, 15 all induced progressive destruction of the brain and caused crises, which endanger the health of human and animals directly. In this regard, the development of a simple, rapid, and sensitive method for prion protein detection before the onset of clinical symptoms is important.…”