title: Iatrogenic and sporadic Creutzfeldt-Jakob disease in 2 sisters without mutation in the prion protein gene.
abstract: Human genetic prion diseases have invariably been linked to alterations of the prion protein (PrP) gene PRNP. Two sisters died from probable Creutzfeldt-Jakob disease (CJD) in Switzerland within 14 y. At autopsy, both patients had typical spongiform change in their brains accompanied by punctuate deposits of PrP. Biochemical analyses demonstrated proteinase K-resistant PrP. Sequencing of PRNP showed 2 wild-type alleles in both siblings. Retrospectively, clinical data revealed a history of dural transplantation in the initially deceased sister, compatible with a diagnosis of iatrogenic CJD. Clinical and familial histories provided no evidence for potential horizontal transmission. This observation of 2 siblings suffering from CJD without mutations in the PRNP gene suggests potential involvement of non-PRNP genes in prion disease etiology.
authors.affiliation: a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;
authors.forename: Karl
authors.initials: K
authors.lastname: Frontzek
authors.affiliation: a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;
authors.forename: Rita
authors.initials: R
authors.lastname: Moos
authors.affiliation: a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;|b Vital-IT group; SIB Swiss Institute of Bioinformatics ; Lausanne , Switzerland;
authors.forename: Elke
authors.initials: E
authors.lastname: Schaper
authors.affiliation: c University Hospital of Psychiatry; Geriatric Psychiatry Clinic; University of Zurich ; Zurich , Switzerland;
authors.forename: Lukas
authors.initials: L
authors.lastname: Jann
authors.affiliation: d Department of Internal Medicine ; University Hospital of Zurich ; Zurich , Switzerland;
authors.forename: Gregor
authors.initials: G
authors.lastname: Herfs
authors.affiliation: e Institute of Clinical Pathology; University Hospital of Zurich ; Zurich , Switzerland.
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Zimmermann
authors.affiliation: a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.affiliation: a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000293:Adolescent; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D007049:Iatrogenic Disease; D009154:Mutation; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D035781:Siblings
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions
keywords: Creutzfeldt-Jakob disease; PRNP; Prion; gene; prion diseases