Prion protein gene codon 129 modulates clinical course of neurological Wilson disease

The polymorphism in the human prion protein gene at codon 129 (PRNP129) determines susceptibility to prion disease, and has been associated with early onset and a more severe course of other neurodegenerative disorders. Here, we tested the hypothesis that PRNPis a disease-modifying gene in clinical Wilson disease with a neurological phenotype. Allele frequencies in patients with clinical Wilson disease were not different from those of a healthy German control population, and PRNP129 genotypes did not result in different serum copper, serum ceruloplasmin, or copper in 24-h urine concentrations. PRNP129 methionine homozygosity, however, led to significantly more severe neurological symptoms in elderly patients, particularly tremor, supporting the notion that PRNP129 homozygosity contributes to neuronal vulnerability.