Table 2.
Mutations, located in the C-terminal region of 3rd helix of prion protein
| Mutation | Family history | AOO (y) | Disease duration | Symptoms | Imaging/neurological |
|---|---|---|---|---|---|
| Glu217Arg44 | Probable positive | 45 | Over 10 years | GSS, with FTD-like symptoms | MRI: mild cortical atrophy affecting the frontal, temporal, and parietal lobes, depigmentation in substania nigra Microscopy: large amyloid plaques with fibrillary cores |
| Tyr218Asn45 | Probable positive | 61 | 6 years | GSS, AD and FTD-like symptoms | EEG: focal frontotemporal slowing during hyperventilation, but no periodic short-wave complexes. PET: asymmetric bifrontal and parieto-occipital hypoperfusion Neuropathology: Spongiform changes, PrPres and Tau pathology |
| Tyr225Cys | Unknown | 59 | 5 years | Atypical CJD | MRI: cortical signal changes in frontotemporoparietal region |
| Tyr226Ter11,46 | Probable positive | 55 | 27 months | AD-like dementia | EEG: generalized slowing and typical pattern of periodic synchronous wave complexes Neuropathology: amyloid deposition, CAA, Tau deposits |
| Gln227Ter11 | Probable positive | 42 | 72 months | FTD, extrapyramidal signs | SPECT: hypoperfusion in the left frontal and temporal cortex Neuropathology: PrP positive plaques, amyloid plaques, neurofibrillary tangles |
Abbreviations: GSS: Gerstmann–Sträussler–Scheinker syndrome; FTD, frontotemporal dementia; MRI, magnetic resonance imaging; AD: Alzheimer’s disease; EEG, electroencephalogram; PET; positron emission tomography; CJD, Creutzfeldt–Jakob disease; AOO, age of onset; CAA, cerebral amyloid angiopathy.