title: Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings.
abstract: Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy-pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.
authors.affiliation: National Reference Centre for Transmissible Spongiform Encephalopathies, Department of Neurology, Georg-August University, Goettingen, Germany. epicjd@med.uni-goettingen.de
authors.forename: Gabi
authors.initials: G
authors.lastname: Schelzke
authors.forename: Sabina
authors.initials: S
authors.lastname: Eigenbrod
authors.forename: Carlos
authors.initials: C
authors.lastname: Romero
authors.forename: Daniela
authors.initials: D
authors.lastname: Varges
authors.forename: Maren
authors.initials: M
authors.lastname: Breithaupt
authors.forename: Ana L
authors.initials: AL
authors.lastname: Taratuto
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D001921:Brain / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology; D004569:Electroencephalography; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions