A VARIANT OF GERSTMANN-STRAUSSLER-SCHEINKER-DISEASE CARRYING CODON-105 MUTATION WITH CODON-129 POLYMORPHISM OF THE PRION PROTEIN GENE - A CLINICOPATHOLOGICAL STUDY

A case was reported of variant Gerstmann-Straussler-Scheinker disease (GSS) carrying codon 105 mutation (Pro to Leu) with codon 129 polymorp hism (Met/Val) of the prion protein (PrP) gene. The male patient had d eveloped clumsiness of the right hand at age 42, and subsequently exhi bited slowly progressive spastic paraparesis, ataxia, dysarthria, memo ry disturbance and apraxia. Myoclonus or periodic synchronous discharg e was not observed. He died at age 53. The cerebral cortex and white m atter showed atrophy, which was prominent in the frontal regions. Ther e were numerous amyloid plaques throughout the cerebral cortex, which were reactive with the antibody to PrP, but not to beta/A4 peptide. Pr P immunostaining also revealed many amorphous deposits in the deep cor tical layers, where neuronal loss and glial proliferation was evident. The cerebellum was almost intact, except a few amyloid plaques in the white matter. This variant GSS with codon 105 mutation has been found in four pedigrees, only in Japan up to the present, and the clinicopa thological phenotype is summarized as follows: (1) onset at age 38-48, with a duration of 7-11 years, (2) prominent spastic paraparesis, ass ociated 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.