Elsevier

Neuroscience Letters

Volume 472, Issue 1, 12 March 2010, Pages 16-18
Neuroscience Letters

No evidence for prion protein gene locus multiplication in Creutzfeldt-Jakob disease

https://doi.org/10.1016/j.neulet.2010.01.043Get rights and content

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.

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Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgements

The Australian National Creutzfeldt-Jakob disease Registry (ANCJDR) is funded by the Commonwealth Department of Health and Ageing. This work was supported in part by an NH&MRC Program Grant (#400202). SJC is supported by an NH&MRC Practitioner Fellowship (#400183) and by an NH&MRC Project Grant (#454546). The Dutch CJD Surveillance is funded by the Dutch Ministry of Health, Welfare and Sports. The ANCJDR and the Dutch Surveillance Center thank the families of all the sporadic CJD patients and

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  • Duplication of amyloid precursor protein (APP), but not prion protein (PRNP) gene is a significant cause of early onset dementia in a large UK series

    2012, Neurobiology of Aging
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    While these studies uncovered an important mutational mechanism at APP, several questions remain about the frequency of these mutations in larger, less selected APP patient cohorts in different countries and the associated phenotypic spectrum. So far as we are aware, PRNP CNV in human prion disease has been explored in only 1 series (Collins et al., 2010). The entire patient cohort consisted of 1531 samples held at the UCL Department of Neurodegenerative Disease.

1

Present address: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds LS2 9JT, United Kingdom.

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