Two patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementianot associated with periodic electroencephalogram; brain PrPres was type 2.
This new mutation extends the list of known pathogenic mutations responsible for genetic CJD, reinforces the clinical heterogeneity of the disease, and advocates for the inclusion of PRNP gene examination in the diagnostic workup of patients with poorly classifiable dementia, even in the absence of family history.
A growing list of phenotypes associated with prion protein loss are coincident with symptoms of neurodegenerative disease and dementia, though it remains contentious whether any such disruption of prion protein function contributes to disease aetiology.
Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP).
Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity.
There was a significant correlation between clinical symptoms and the neuroanatomical distribution of prion protein-immunoreactive aggregates, i.e. subtentorial predominance in ataxia vs cortical predominance in dementia.
Investigation of these patients, including two with neuropathologically verified AD and one with post-mortem confirmed CJD, did not reveal an alternative aetiology for their dementia.
The APOBEC-related mutations were higher in healthy controls than in cases suffering from neurodegeneration, with the exception of the dementia group with the prion protein gene (PRNP) MV genotype.
Patients with an alternative diagnosis and those with sCJD were of similar age, sex and frequency of dementia but CJD mimics had a longer clinical history.
A two-octapeptide repeat deletion of the prion protein gene has been recently observed in a patient with a 2-year history of dementia and a clinical diagnosis of possible Creutzfeldt-Jakob disease (CJD).
We studied whether codon 129 polymorphism of the PrP gene modulates the presence of tau- and Abeta-associated lesions among 188 patients over 70 years of age without evidence of dementia.
We present the clinical and neuropathological features of a family with an early and long-standing dementia manifesting with posterior cortical atrophy and related to a 120 bp insertional mutation of the prion protein gene.
GSS, associated with a missense mutation at codon 102 of the prion protein (PrP) gene (GSS102), is a hereditary disorder that presents with progressive ataxia and dementia, and is characterized by the loss of deep tendon reflexes and painful dysesthesias of the legs in its early stage.
Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia.