Unusual Clinical and Molecular-Pathological Profile of Gerstmann-Straussler-Scheinker Disease Associated With a Novel PRNP Mutation (V176G)

IMPORTANCE Here we describe the unusual clinical and molecular-neuropathological profile of a case of Gerstmann-Str ussler-Scheinker disease associated with a novel prion protein (PRNP) gene mutation. OBSERVATIONS This case report from the Australian National Creutzfeldt-Jakob Disease Registry concerns a 61-year-old British-born woman with no history of neurodegenerative disorder in first-degree relatives. Rapidly progressive dementia, altered behavior, and cerebellar ataxia dominated the clinical picture in the period immediately following minor elective surgery, with death 1 month later in an akinetic-mute state. Brain histopathological examination revealed neuronal loss, scant foci of spongiform change, and diffuse multicentric amyloid plaques, selectively immunoreactive for prion protein, within the cerebral and cerebellar cortices and deep gray matter. Tau immune-reactive neurofibrillary tangles and neuritic threads were present in the cerebral cortex. PRNP sequencing demonstrated a valine to glycine mutation at codon 176, with valine homozygosity at polymorphic codon 129. Western-blot analysis of frozen brain tissue displayed a nonclassic protease-resistant prion protein banding pattern, with a prominent approximately 8-kDa protease-resistant fragment. CONCLUSIONS AND RELEVANCE Reported is a proband with a novel PRNP mutation associated with neuropathologically confirmed Gerstmann-Str ussler-Scheinker disease displaying a somewhat unusual constellation of clinicopathological features, which overall subserve to further broaden an already diverse phenotypic spectrum.