TY - JOUR
T1 - Prion protein gene codon 129 modulates clinical course of neurological Wilson disease
AU - Grubenbecher, Stephanie
AU - Stüve, Olaf
AU - Hefter, Harald
AU - Korth, Carsten
PY - 2006/4/1
Y1 - 2006/4/1
N2 - The polymorphism in the human prion protein gene at codon 129 (PRNP 129) 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 PRNP is 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 PRNP 129 genotypes did not result in different serum copper, serum ceruloplasmin, or copper in 24-h urine concentrations. PRNP 129 methionine homozygosity, however, led to significantly more severe neurological symptoms in elderly patients, particularly tremor, supporting the notion that PRNP 129 homozygosity contributes to neuronal vulnerability.
AB - The polymorphism in the human prion protein gene at codon 129 (PRNP 129) 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 PRNP is 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 PRNP 129 genotypes did not result in different serum copper, serum ceruloplasmin, or copper in 24-h urine concentrations. PRNP 129 methionine homozygosity, however, led to significantly more severe neurological symptoms in elderly patients, particularly tremor, supporting the notion that PRNP 129 homozygosity contributes to neuronal vulnerability.
KW - Copper metabolism
KW - Genotype-phenotype correlations
KW - Neurodegenerative diseases
KW - Neuronal vulnerability
KW - Polymorphism
KW - Prion protein
KW - Tremor
KW - Wilson disease
UR - http://www.scopus.com/inward/record.url?scp=33645130155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645130155&partnerID=8YFLogxK
U2 - 10.1097/01.wnr.0000209006.48105.90
DO - 10.1097/01.wnr.0000209006.48105.90
M3 - Article
C2 - 16543824
AN - SCOPUS:33645130155
SN - 0959-4965
VL - 17
SP - 549
EP - 552
JO - NeuroReport
JF - NeuroReport
IS - 5
ER -