| Research Abstract |
Recent molecular genetic studies revealed that the human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to a distinct type of prion diseases. On this project, we found out 6 new mutations and 3 insertional mutations of PrP gene. It is useful to classify prion diseases into plaque type or non-plaque type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 102/219, codon 105, codon 129 Valine, codon 145 and insertional polymorphisms belong to the plaque type prion diseases, whereas the wild-type PrP (codon 129 Methionine) and the variants including codon 180, codon 200, and codon 232 mutations belong to the non-plaque type (synaptic type). The non-plaque type prion diseases showed a rapidly progressive dementia, myoclonus and periodic synchronous discharges in the electroencephalogram, and in the pathological findings diffuse gray matter PrP accumulations including the synaptic structures. The plaque type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposits in the central nervous system influences the clinical and pathological aspects of prion diseases. Thus, PrP accumulations may play a central role in the pathogenesis of prion diseases.
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