A Second Case of Gerstmann-Straussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient

A rare case of Gerstmann-Straussler-Scheinker disease in a 36-year-old Dutch man is reported. The clinical phenotype was characterized by slowly progressive cognitive decline, later followed by ataxia and parkinsonism. Neuropathologic findings consisted of numerous amyloid plaques in the cerebellum, which showed positive staining for the abnormal prion protein (PrP(Sc)). In addition, there were tau accumulations around numerous amyloid deposits in the cerebral cortex, striatum, hippocampal formation, and midbrain. There was no spongiform degeneration. Western blot analysis showed the co-occurrence of 2 distinct abnormal prion protein species comprising an unglycosylated, protease-resistant fragment of approximately 8 kd, which was found to be truncated at both N- and C-terminal ends by epitope mapping, and a detergent-insoluble but protease-sensitive form of full-length PrP(Sc). Sequence analysis disclosed a mutation at codon 131 of the prion protein gene (PRNP), resulting in a valine-for-glycine substitution (G131V). The patient was heterozygous at the polymorphic codon 129 and carried the mutation on the methionine allele. To our knowledge, this is the second family worldwide in which this mutation has been identified. Gerstmann-Straussler-Scheinker disease should be considered in patients with a clinical diagnosis of familial frontotemporal dementia.