An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease

Essential Role of the Prion Protein N Terminus in Subcellular Trafficking and Half-life of Cellular Prion Protein

“…In light of the results reported here, these findings could also be explained by altered intracellular trafficking of the mutated PrP because of the alterations in the N-terminal part. Clinical studies have shown that two to nine octapeptides in addition to the normal five segregate with familial forms of Creutzfeldt-Jakob disease (46,47) and nontransmissible prion disease in transgenic mice (48). Studies addressing the effect of these mutations on subcellular trafficking are in progress.…”

Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

“…Additional octarepeats have been identified in patients suffering from familial CJD (Owen et al, 1990(Owen et al, , 1992Goldfarb et al, 1991Goldfarb et al, , 1993Campbell et al, 1996). PrP encompassing nine additional octarepeats associated with familial CJD failed to undergo Cu 2 + -mediated endocytosis, suggesting that neurodegeneration may arise from the ablation of internalization due to mutation of the octarepeats (Sumudhu et al, 2001).…”

“…A series of mutations affect the octarepeat region of the prion protein. fCJD patients encompassing two (Goldfarb et al, 1993), four (Campbell et al, 1996), five (Goldfarb et al, 1991), six (Owen et al, 1990), seven (Goldfarb et al, 1991), eight (Goldfarb et al, 1991) and nine additional octarepeats (Owen et al, 1992) have been described. All these patients are heterozygous regarding these mutations (Majtenyi et al, 2000).…”

Prion disease genetics

“…This mutation has some historical importance as it was the first described PRNP mutation, in a small UK family. 3 Genealogical work by Poulter and Collinge 63 in 1992 demonstrated a common ancestor of this small family and a larger pedigree with over 50 affected individuals. In 2005, this pedigree comprised over 80 affected individuals and 100 at-risk of disease affording a detailed analysis of phenotype and its determinants.…”

“…Perhaps most prominent among these was the linkage to chromosome 20 and mutation discovery in PRNP in families with dominantly inherited neurodegenerative diseases. 3,4 The fact that heterogeneous diseases caused by mutation of PRNP were known to be transmissible to laboratory animals obviated the need to the search for a cryptic infectious organism. A great deal is now known about the inherited prion diseases (IPD) as molecular genetic diagnosis has been available for over a decade.…”