Mutations in NR4A2 associated with familial Parkinson disease. Academic Article uri icon

Overview

abstract

  • NR4A2, encoding a member of nuclear receptor superfamily, is essential for the differentiation of the nigral dopaminergic neurons. To determine whether NR4A2 is a susceptibility gene for Parkinson disease, we carried out genetic analyses in 201 individuals affected with Parkinson disease and 221 age-matched unaffected controls. We identified two mutations in NR4A2 associated with Parkinson disease (-291Tdel and -245T-->G), which map to the first exon of NR4A2 and affect one allele in 10 of 107 individuals with familial Parkinson disease but not in any individuals with sporadic Parkinson disease (n = 94) or in unaffected controls (n = 221). The age at onset of disease and clinical features of these ten individuals were not different from those of individuals with typical Parkinson disease. The mutations resulted in a marked decrease in NR4A2 mRNA levels in transfected cell lines and in lymphocytes of affected individuals. Additionally, mutations in NR4A2 affect transcription of the gene encoding tyrosine hydroxylase. These data suggest that mutations in NR4A2 can cause dopaminergic dysfunction, associated with Parkinson disease.

publication date

  • December 23, 2002

Research

keywords

  • DNA-Binding Proteins
  • Genetic Predisposition to Disease
  • Mutation
  • Parkinson Disease
  • Transcription Factors

Identity

Scopus Document Identifier

  • 0037226797

Digital Object Identifier (DOI)

  • 10.1038/ng1066

PubMed ID

  • 12496759

Additional Document Info

volume

  • 33

issue

  • 1