title: No evidence for prion protein gene locus multiplication in Creutzfeldt-Jakob disease.
abstract: Precedent of causative multiplication of key gene loci exists in familial forms of both Alzheimer's and Parkinson's diseases. Genetic Creutzfeldt-Jakob disease (CJD) is often clinically indistinguishable from sporadic disease and inexplicably, a negative family history of a similar disorder occurs in around 50-90% of patients harboring the most common, disease-associated, prion protein gene (PRNP) mutations. We undertook semi-quantitative analysis of the PRNP copy number in 112 CJD patients using quantitative polymerase chain reaction. All included cases satisfied classification criteria for probable or definite sporadic CJD, ascertained as part of longstanding, prospective, national surveillance activities. No examples of additional copies of the PRNP locus as an explanation for their disease was found in any of the 112 sporadic CJD patients. Hence, contrasting with more common, age-related neurodegenerative diseases, the genetic aetiology in human prion disease continues to appear entirely restricted to small scale mutations within a single gene, with no evidence of multiplication of this validated candidate gene locus as a cause.
authors.affiliation: Australian National CJD Registry, Department of Pathology, The University of Melbourne, Parkville 3010, Australia. stevenjc@unimelb.edu.au
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Collins
authors.forename: Maaike
authors.initials: M
authors.lastname: Schuur
authors.forename: Alison
authors.initials: A
authors.lastname: Boyd
authors.forename: Victoria
authors.initials: V
authors.lastname: Lewis
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Klug
authors.forename: Amelia
authors.initials: A
authors.lastname: McGlade
authors.forename: Andrew
authors.initials: A
authors.lastname: van Oosterhout
authors.forename: Guido
authors.initials: G
authors.lastname: Breedveld
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Colin
authors.initials: C
authors.lastname: Masters
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Van Duijn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions