NR4A2 (from Dekker MC et al. 2003 and Chung KK et al. 2003)
A recent report described two mutations in the NR4A2, or NURR1 gene (Le et al., 2003). The clinical phenotype in the patients with mutations in NR4A2 was concordant with lateonset Parkinson's disease without atypical features. Radiological or neuropathological data are not available. NR4A2 (chromosome 2q22-23) is a gene involved in the differentiation and maintenance of dopaminergic neurons. Due to its function, previous studies had already suggested NR4A2 to be a candidate gene for Parkinson's disease (Zetterstrom et al., 1996; Le et al., 1999).
NR4A2 was studied in a series of 107 individuals with familial Parkinson's disease (70 of whom had a history of Parkinson's disease over at least two generations). Two heterozygous mutations (-291Tdel and -245T®G) were revealed in 10 individuals, who were all of European descent. Both mutations affect a non-coding exon (exon 1) of the gene and lead to a marked decrease in NR4A2 mRNA levels. The mechanism by which this mRNA transcription is targeted is not yet clear.