Background: The clinical heterogeneity of Wilson disease expression cannot be fully explained by the various mutations of the Wilson disease gene. The prion-related protein (PrP) has been shown to bind copper in vitro and might therefore influence Wilson disease.
Objective: To examine the effect of the PrP polymorphism at codon 129, resulting in either methionine or valine (M129V), on the clinical phenotype of patients with Wilson disease.
Design and setting: Retrospective cross-sectional study at a university hospital.
Participants: A total of 134 patients were grouped according to their PrP M129V genotypes and initial clinical symptoms (hepatic vs neurological).
Results: The onset of symptoms was significantly delayed in patients homozygous for the 129M allele as compared with patients with at least 1 V allele (mean +/- SD age, 20.90 +/- 11.9 years vs 15.5 +/- 7.6 years; P = .003). No significant correlation was found when analyzing the impact of the PrP M129V genotype on the clinical symptoms at initial manifestation (hepatic vs neurological; P = .44).
Conclusion: This study shows for the first time, to our knowledge, that the human PrP polymorphism M129V influences the onset of symptoms in patients with the copper storage disorder Wilson disease.