Gerstmann-Straüssler-Scheinker disease: novel PRNP mutation and VGKC-complex antibodies
Matthew Jones1, Sola Odunsi1, Daniel du Plessis1
1From 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.
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.
Conclusion:
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.
More Related Videos
06:02Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018