[Molecular genetics in Creutzfeldt-Jakob disease]

Recent molecular genetic studies revealed that human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to the distinct type of prion diseases. We report herein that it is useful to classify prion diseases into Creutzfeldt-Jakob disease (CJD) type or Gerstmann-Sträussler syndrome (GSS) type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 105, codon 129, codon 145 and insertional mutations belong to the GSS type, while the wild type PrP and the variants including codon 180, codon 200, codon 210, and codon 232 mutations belong to the CJD type. The CJD type prion diseases showed a rapidly progressive dementia, myoclonus, and periodic synchronous discharges in the electroencephalogram, and showed diffuse gray matter PrP accumulations including the synaptic structures in the pathological findings. The GSS 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 deposit in the central nervous system influences the clinical and pathological aspects of prion diseases.