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Translated mutation in the Nurr1 gene as a cause for Parkinson's disease

Authors

  • David A. Grimes MD,

    Corresponding author
    1. Department of Medicine, Division of Neurology, Ottawa Hospital, Ottawa, Ontario, Canada
    2. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
    • Ottawa Hospital, Civic Campus, 1053 Carling Avenue, Ottawa, K1Y 4E9, Canada

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    • Drs. Grimes and Han contributed equally to this study.

  • Fabin Han MD,

    1. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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    • Drs. Grimes and Han contributed equally to this study.

  • Michel Panisset MD,

    1. Department of Neurology, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada
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  • Lemuel Racacho BSc,

    1. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Fengxia Xiao PhD,

    1. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Ruobing Zou,

    1. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Kelly Westaff,

    1. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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  • Dennis E. Bulman PhD

    1. Department of Medicine, Division of Neurology, Ottawa Hospital, Ottawa, Ontario, Canada
    2. Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, Ontario, Canada
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Abstract

Multiple genes have been now identified as causing Parkinson's disease (PD). In 2003, two mutations were identified in exon 1 of the Nurr1 gene in 10 of 107 individuals with familial PD. To date, investigators have only focused on screening for these known mutations of the Nurr1 gene. All individuals were recruited from two Parkinson's disease clinics in Canada. Following PCR amplification of each exon of the Nurr1 gene, samples underwent denaturing high-performance liquid chromatography (DHPLC) analysis. Ten individuals also underwent direct sequencing as well as any samples where variants were identified. The Nurr1 gene was evaluated for 202 PD individuals, 37% of whom had at least one relative with PD and 100 control non-PD individuals. Using DHPLC and direct sequencing, we did not detect any sequence variants in exon 1. Variants in amplicon 6 were seen and direct sequencing confirmed a known NI6P polymorphism in intron 6. Novel polymorphisms were also identified in exon 3 and intron 5. A novel mutation was identified in exon 3 in one nonfamilial PD individual. This heterozygous C-to-G transversion resulted in a serine-to-cysteine substitution and was not identified in any of the other 602 chromosomes screened. Mutations in the Nurr1 gene in our large cohort of familial and sporadic PD individuals are rare. The novel mutation in exon 3 is predicted to affect phosphorylation and functional studies to assess this are underway. This is the first coding mutation identified in the Nurr1 gene for Parkinson's disease. © 2006 Movement Disorder Society

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