A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker disease

Background: Gerstmann-Straussler-Scheinker disease is a rare form of prion disease. Objective: To determine the prion mutation in a 51-year-old man without a family history of neurologic disease who died from Gerstmann-Straussler-Scheinker disease. Patient and Methods: The patient was a 51-year-old man who died after a 9-year illness characterized by dementia and eventually ataxia. Neuropathologic studies were performed, the results of which revealed abundant prion protein-immunopositive amyloid plaques in the cerebellum without spongiform degeneration. Results: Genetic analysis of the prion protein gene showed a novel mutation at codon 131 that caused a valine-for-glycine substitution (G131V) and homozygosity at codon 129 (129M). Proteinase K-resistant prion protein was detected by Western blot analysis. Conclusions: This is the first mutation described in the short, antiparallel P-sheet domain of the prion protein. This report highlights the importance of genetic analysis of patients with atypical dementia even in the absence of a family history.