Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease.
This variant GSS with codon 105 mutation has been found in four pedigrees, only in Japan up to the present, and the clinicopathological phenotype is summarized as follows: (1) onset at age 38-48, with a duration of 7-11 years, (2) prominent spastic paraparesis, associated with dementia and ataxia, (3) numerous amyloid plaques in the cerebral cortex, (4) amorphous PrP deposits with neuronal loss in the deep cortical layers, and (5) minor change of cerebellum.
In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopathological phenotype of Creutzfeldt-Jakob disease (CJD).
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).
GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); these conditions show a broad spectrum of clinical presentation, the main signs being ataxia, spastic paraparesis, extrapyramidal signs and dementia.
Using this system, we found a new mutation of the PrP gene in a patient with pathologically confirmed Creutzfeldt-Jakob disease and a negative family history for dementia.
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.
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.
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.
Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia.
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.
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 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".
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.