title: Gerstmann-Straüssler-Scheinker disease: novel PRNP mutation and VGKC-complex antibodies.
abstract: OBJECTIVE
  To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs).
  
  
  METHODS
  Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene.
  
  
  RESULTS
  The patient was diagnosed in life with VGKC-complex Ab-associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found.
  
  
  CONCLUSIONS
  VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease.
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jones
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Sola
authors.initials: S
authors.lastname: Odunsi
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: du Plessis
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bishop
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK. dg28.2.02@live.co.uk.
authors.forename: David
authors.initials: D
authors.lastname: Gow
mesh_terms: D000906:Antibodies / Q000009:adverse effects / Q000097:blood*; D004660:Encephalitis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D017809:Fatal Outcome; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: D000906:Antibodies; C512656:PRNP protein, human; D024642:Potassium Channels, Voltage-Gated; D000072002:Prion Proteins; D011328:Prions