, Volume 18, Issue 1, pp 13-19
Date: 30 Jan 2008

PRNP M129V homozygosity in multiple system atrophy vs. Parkinson’s disease

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Abstract

Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown etiology characterized by extrapyramidal, pyramidal, cerebellar, and autonomic dysfunction in any combination. We report a patient with a 4-year history of MSA who developed dementia associated with sporadic Creutzfeldt–Jakob disease (CJD). Our proband was MM homozygous for the M129V polymorphism within the prion protein gene (PRNP), a known risk factor for CJD. We conducted a case–control study to test the hypothesis that homozygosity for the M129V polymorphism of PRNP occurs more frequently in MSA in comparison to Parkinson’s disease and healthy volunteers. A total of 63 patients with MSA, 54 age-, race- and gendermatched controls with Parkinson’s disease, and 126 matched healthy volunteers were studied. The genotype analysis revealed no significant difference in the codon 129 genotype distribution in MSA as compared to controls. Nonetheless, the frequencies of the MM and VV genotypes were higher in MSA than in Parkinson’s disease. Thus, homozygosity, particularly VV homozygosity, at codon 129 of PRNP is associated with MSA compared to a clinically related but pathophysiologically distinct α-synucleinopathy. Considering the possibility that the prion protein contributes to the pathogenesis of MSA would require confirmation of these findings in an independent patient population.