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BMC Med Genet. 2016 Apr 7;17:28. doi: 10.1186/s12881-016-0278-2.

Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study.

Author information

1
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
2
Clinical Dementia Center, Department of Neurology, Georg-August University Göttingen, Göttingen, Germany.
3
German Center for Neurodegenerative Diseases, Gottingen, Germany.
4
Department of Pathology, Case Western Reserve University, Cleveland, OH, 44060, USA.
5
MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK. s.mead@prion.ucl.ac.uk.

Abstract

BACKGROUND:

Human prion diseases are relentlessly progressive neurodegenerative disorders which include sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). Aside from variants of the prion protein gene (PRNP) replicated association at genome-wide levels of significance has proven elusive. A recent association study identified variants in or near to the PLCXD3 gene locus as strong disease risk factors in multiple human prion diseases. This study claimed the first non-PRNP locus to be highly significantly associated with prion disease in genomic studies.

METHODS:

A sub-study of a genome-wide association study with imputation aiming to replicate the finding at PLCXD3 including 129 vCJD and 2500 sCJD samples. Whole exome sequencing to identify rare coding variants of PLCXD3.

RESULTS:

Imputation of relevant polymorphisms was accurate based on wet genotyping of a sample. We found no supportive evidence that PLCXD3 variants are associated with disease.

CONCLUSION:

The marked discordance in vCJD genotype frequencies between studies, despite extensive overlap in vCJD cases, and the finding of Hardy-Weinberg disequilibrium in the original study, suggests possible reasons for the discrepancies between studies.

KEYWORDS:

Creutzfeldt-Jakob disease; Human prion diseases; PLCXD3

PMID:
27055460
PMCID:
PMC4823897
DOI:
10.1186/s12881-016-0278-2
[Indexed for MEDLINE]
Free PMC Article

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