FAMILIAL SPONGIFORM ENCEPHALOPATHY ASSOCIATED WITH A NOVEL PRION PROTEIN GENE MUTATION

Human prion diseases include Creutzfeldt-Jakob disease, Gerstmann-Strl ussler-Scheinker disease, fatal familial insomnia, and kuru, Each of t hese diseases has a specific clinical presentation while spongiform en cephalopathy, neuronal loss, and gliosis are their neuropathological h allmarks. We studied a Brazilian family with an autosomal dominant for m of dementia, Nine members of the family were affected by a dementia with frontotemporal clinical features, with a mean age at onset of 44. 8 +/- 3.8 years and a mean duration of symptoms of 4.2 +/- 2.4 years. Neuropathological examination of 3 patients showed severe spongiform c hange and neuronal loss in the deep cortical layers and in the putamen , but minimal gliosis in the most severely affected areas, The putamen and cerebellum, but not other areas of the affected brain, displayed prion protein immunoreactivity. A novel prion protein gene mutation ca using a nonconservative substitution at codon 183 was identified in 2 neuropathologically confirmed affected individuals (mother and son). T he mutation was transmitted in a mendelian fashion to 12 members of th e family, Therefore, we identified a novel prion disease variant chara cterized by an early onset and long duration of the symptoms, severe s pongiform change with minimal gliosis, associated with a prion protein gene mutation at codon 183.