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

Stephanie Grubenbecher1, Olaf Stüve, Harald Hefter

  • 1Institute for Neuropathology, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.

Neuroreport
|March 18, 2006
PubMed

Insights

The human prion protein gene (PRNP) polymorphism at codon 129 influences neurodegenerative disease severity. PRNP 129 methionine homozygosity is linked to more severe neurological symptoms in Wilson disease patients, particularly tremor.

Area of Science:

  • Neurogenetics
  • Neurology
  • Human Genetics

Background:

  • The human prion protein gene polymorphism at codon 129 (PRNP 129) is a known factor influencing susceptibility and disease course in prion diseases.
  • This polymorphism has also been linked to earlier onset and increased severity in other neurodegenerative conditions.

Purpose of the Study:

  • To investigate the role of the PRNP gene as a potential disease-modifying factor in patients with clinical Wilson disease presenting with neurological symptoms.
  • To determine if PRNP 129 genotypes correlate with disease severity or specific biochemical markers in Wilson disease.

Main Methods:

  • Genotyping of the PRNP 129 polymorphism in a cohort of patients with clinical Wilson disease and a healthy German control population.
  • Analysis of allele frequencies and correlation of PRNP 129 genotypes with clinical neurological assessments and biochemical parameters (serum copper, ceruloplasmin, urinary copper).

Main Results:

  • Allele frequencies for PRNP 129 did not differ significantly between Wilson disease patients and controls.
  • No significant differences in serum copper, serum ceruloplasmin, or 24-h urinary copper concentrations were observed across different PRNP 129 genotypes.
  • A significant association was found between PRNP 129 methionine homozygosity and more severe neurological symptoms, especially tremor, in elderly Wilson disease patients.

Conclusions:

  • The PRNP 129 polymorphism does not appear to influence copper metabolism markers in Wilson disease.
  • PRNP 129 methionine homozygosity may contribute to increased neuronal vulnerability, exacerbating neurological symptoms in aging Wilson disease patients.
  • This suggests a disease-modifying role for PRNP 129 in the neurological phenotype of Wilson disease.

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