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.
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.
Gerstmann-Sträussler-Scheinker syndrome caused by the P102L mutation in the prion protein gene (GSS102) is usually characterized by the onset of slowly progressive cerebellar ataxia, with dementia occurring much later.
We developed gene panel based technologies to assess 16 genes known to harbour mutations causal of dementia and combined these with PCR based assessments of the C9orf72 hexanucleotide repeat expansion and the octapeptide repeat region of PRNP.
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.
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.
Screening for mutations in the PRNP gene should be performed in all diagnosed cases of prion disease and in cases of familial occurrence of early onset dementia of unknown aetiology.
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.
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.
This case supports the pathogenicity of the T188 PRNP mutation, demonstrates the variability of clinical phenotypes associated with certain mutations, and emphasizes the importance of testing for genetic prion disease in cases of apparently sporadic atypical dementia.
In this study, we screened the PRNP gene to evaluate the frequency of PRNP mutations and their correlations with clinical phenotype in 185 sporadic neurodegenerative dementia cases and 310 control subjects.
The psychiatric symptoms in young patients with sCJD are similar to the psychiatric symptoms expressed by patients with variant CJD; however, in contrast with the variant cases, young patients with sCJD experience development of prominent dementia early in the disease course.
GSS is defined as a neurodegenerative disease "in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multi-centric PrP plaques".
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.