title: Polymorphisms within the prion-like protein gene (Prnd) and their implications in human prion diseases, Alzheimer's disease and other neurological disorders.
abstract: Only 10% of human transmissible spongiform encephalopathies (TSEs) are associated with mutations of the Prnp region encoding the prion protein (PrP). Recently, the murine PrP-like protein doppel (Dpl) was described and was shown to be overexpressed in certain strains of PrP knockout mice and to cause neurological diseases such as ataxia and Purkinje cell loss. To answer the question of whether there are any polymorphisms within the PrP-like protein gene (Prnd) that might cause or be involved in the development of TSEs, we investigated the complete open reading frame of the human Prnd gene from 58 patients who had died of genetic or sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease or other neurological disorders and from 111 controls. We found five new polymorphisms and one frame shift mutation. One silent polymorphism, which does not lead to an altered amino acid sequence, was also observed. Statistical analysis revealed a significant difference in the distribution of the Prnd genotype at codon 174 between sporadic CJD patients and healthy controls.
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, Department of Virology, Division of TSE-Research 2/02, 63225 Langen, Germany. schroebj@ing.boehringer-ingelheim.de
authors.forename: B
authors.initials: B
authors.lastname: Schröder
authors.forename: B
authors.initials: B
authors.lastname: Franz
authors.forename: P
authors.initials: P
authors.lastname: Hempfling
authors.forename: M
authors.initials: M
authors.lastname: Selbert
authors.forename: T
authors.initials: T
authors.lastname: Jürgens
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: M
authors.initials: M
authors.lastname: Bodemer
authors.forename: S
authors.initials: S
authors.lastname: Poser
authors.forename: I
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D058851:GPI-Linked Proteins; D005838:Genotype; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics*; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics*
chemical_list: D058851:GPI-Linked Proteins; C501125:PRND protein, human; D011328:Prions; C122036:Prnd protein, mouse; D004247:DNA