title: Unusual clinical and molecular-pathological profile of gerstmann-Sträussler-Scheinker disease associated with a novel PRNP mutation (V176G).
abstract: OBJECTIVE
  Here we describe the unusual clinical and molecular-neuropathological profile of a case of Gerstmann-Sträussler-Scheinker disease associated with a novel prion protein (PRNP) gene mutation.
  
  
  METHODS
  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
  Reported is a proband with a novel PRNP mutation associated with neuropathologically confirmed Gerstmann-Sträussler-Scheinker disease displaying a somewhat unusual constellation of clinicopathological features, which overall subserve to further broaden an already diverse phenotypic spectrum.
authors.affiliation: Department of Pathology, University of Melbourne, Victoria, Australia2Australian National Creutzfeldt-Jakob Disease Registry, University of Melbourne, Victoria, Australia.
authors.forename: Marion
authors.initials: M
authors.lastname: Simpson
authors.forename: Vanessa
authors.initials: V
authors.lastname: Johanssen
authors.forename: Alison
authors.initials: A
authors.lastname: Boyd
authors.forename: Genevieve
authors.initials: G
authors.lastname: Klug
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: Roger
authors.initials: R
authors.lastname: Pamphlett
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.forename: Victoria
authors.initials: V
authors.lastname: Lewis
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Collins
mesh_terms: D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D016098:Gerstmann-Straussler-Scheinker Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005998:Glycine / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D010641:Phenotype; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D014633:Valine; D005998:Glycine