Abstract: The identification of mutations in NURR1 provides molecular tools for the development of diagnostic, prophylactic and therapeutic agents for Parkinson's Disease. In specific embodiments, two point mutations are identified in exon 1 of the NURR1 gene in 10/107 (9.3%) cases of familial Parkinson's disease (PD). The mutations reduce NURR1 gene expression (mRNA and protein levels) by 87–95% and decrease tyrosine hydroxylase (a rate-limited dopamine synthesis enzyme) gene expression in vitro. It is also demonstrated that in vivo NURR1 mRNA levels in the lymphocytes from the PD patients with the exon 1 mutation are reduced by 68–84%, and in over 50% sporadic PD patients the NURR1 mRNA levels in lymphocytes are significantly reduced. A homozygous polymorphism is identified in intron 6 of NURR1 that correlates with the presence of Parkinson's disease. A splicing variant in NURR1 exon 5 is identified.

Abstract: The identification of mutations in NURR1 provides molecular tools for the development of diagnostic, prophylactic and therapeutic agents for Parkinson's Disease. In specific embodiments, two point mutations are identified in exon 1 of the NURR1 gene in 10/107 (9.3%) cases of familial Parkinson's disease (PD). The mutations reduce NURR1 gene expression (mRNA and protein levels) by 87-95% and decrease tyrosine hydroxylase (a rate-limited dopamine synthesis enzyme) gene expression in vitro. It is also demonstrated that in vivo NURR1 mRNA levels in the lymphocytes from the PD patients with the exon 1 mutation are reduced by 68-84%, and in over 50% sporadic PD patients the NURR1 mRNA levels in lymphocytes are significantly reduced. A homozygous polymorphism is identified in intron 6 of NURR1 that correlates with the presence of Parkinson's disease. A splicing variant in NURR1 exon 5 is identified.