Age at onset of genetic (E200K) and sporadic Creutzfeldt-Jakob diseases is modulated by the CYP4X1 gene

Journal of Neurology, Neurosurgery, and Psychiatry
Anna PoleggiMaurizio Pocchiari

Abstract

The Glu to Lys change at codon 200 (E200K) of the PRNP gene is the most frequent mutation associated to genetic Creutzfeldt-Jakob disease (CJD) and the only one responsible for geographical clusters. Patients carrying this mutation develop disease at different ages and show variable clinical phenotypes that are not affected by the methione/valine polymorphism at codon 129 of the PRNP gene suggesting the influence of other factors. The objective of this study is to look for genes other than PRNP that might be responsible of this variability. We searched for other genes by performing genome-wide analyses (GWA) on 19 patients with genetic CJD and 18 healthy subjects carrying the E200K mutation of PRNP and belonging to the Calabrian cluster in Italy. We then validate this result in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD referred to the Italian CJD national registry. We identified two single nucleotide polymorphisms on the CYP4X1 gene locus as candidate disease modifiers in patients with E200K CJD of the cluster area and confirmed this finding in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD. Our results indicate that the CYP4X1 gene modulates the o...Continue Reading

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Citations

Sep 21, 2019·Annual Review of Genetics·Simon MeadJohn Collinge
Jan 5, 2019·Acta Neuropathologica Communications·Giuseppe Di FedeGiorgio Giaccone
Feb 4, 2021·Acta Neuropathologica·Jean-Yves DouetOlivier Andreoletti
Jun 23, 2020·Neurobiology of Disease·Emma Jones, Simon Mead
Apr 4, 2021·International Journal of Molecular Sciences·Viktor HlaváčPavel Souček

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