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Splice site SNPs of phospholipase PLCXD3 are significantly associated with variant and sporadic Creutzfeldt-Jakob disease

Matthew T Bishop1*, Pascual Sanchez-Juan2 and Richard SG Knight1

Author Affiliations

1 National CJD Research & Surveillance Unit, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

2 Neurology Department, University Hospital “Marqués de Valdecilla”. Fundación “Marqués de Valdecilla” (University of Cantabria) IFIMAV and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain

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BMC Medical Genetics 2013, 14:91  doi:10.1186/1471-2350-14-91

Published: 12 September 2013



Variant Creutzfeldt-Jakob disease is an infectious, neurodegenerative, protein-misfolding disease, of the prion disease family, originally acquired through ingestion of meat products contaminated with bovine spongiform encephalopathy (BSE). Public health concern was increased by the discovery of human-to-human transmission via blood transfusion. This study has verified a novel genetic marker linked to disease risk.


SNP imputation and association testing indicated those genes that had significant linkage to disease risk and one gene was investigated further with Sanger resequencing. Results from variant Creutzfeldt-Jakob disease were compared with those from sporadic (idiopathic) Creutzfeldt-Jakob disease and published controls.


The most significant disease risk, in addition to the prion protein gene, was for the phosphatidylinositol-specific phospholipase C, X domain containing 3 (PLCXD3) gene. Sanger resequencing of CJD patients across a region of PLCXD3 with known variants confirmed three SNPs associated with variant and sporadic CJD.


These data provide the first highly significant confirmation of SNP allele frequencies for a novel CJD candidate gene providing new avenues for investigating these neurodegenerative prion diseases. The phospholipase PLCXD3 is primarily expressed in the brain and is associated with lipid catabolism and signal transduction.

Prion disease; Infection; Neurodegeneration; Susceptibility; Phospholipase