Further extension of the H1 haplotype associated with progressive supranuclear palsy

Authors

  • Pau Pastor MD, PhD,

    Corresponding author
    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
    • Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 South Euclid Ave., St. Louis, MO 63110
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  • Mario Ezquerra MD, PhD,

    1. Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Eduardo Tolosa MD, PhD,

    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Esteban Muñoz MD, PhD,

    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • María José Martí MD, PhD,

    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Francesc Valldeoriola MD, PhD,

    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • José Luís Molinuevo MD, PhD,

    1. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Malalties del Sistema Nerviós. Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Matilde Calopa MD, PhD,

    1. Neurology Service, Hospital de Bellvitge, Barcelona, Spain
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  • Rafael Oliva MD, PhD

    1. Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain
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Abstract

The recent finding of disequilibrium among several polymorphisms along the tau gene and the strong association of one of the two haplotypes formed by these polymorphisms (H1) with progressive supranuclear palsy (PSP) suggests that a single allele in or near the tau gene at 17q21 is responsible for increased risk in most of the PSP cases. We sought to determine whether mutations in the tau gene are responsible for the disease in 45 sporadic PSP patients. Furthermore, we analyzed some markers located in the common region of linkage (D17S800-D17S791), associated with some cases of familial frontotemporal dementia (FTDP-17), and the SNPs rs1816 and rs937 close to the tau gene, to determine their possible association with sporadic PSP. We did not find pathogenic mutations in exons 9, 10, 12, or 13 of the tau gene, indicating that tau mutations in both the splice-site region of the exon 10 and in the microtubule-binding region of tau gene are not a cause of PSP in this study group. We found significant overrepresentation of the haplotypes H1, extended up to the promoter of the tau gene (H1P), in PSP patients as compared with controls. In addition, a significant overrepresentation of the D17S810 2/2 and 3/2 genotypes, of the SNP rs1816 A/A, and of the SNP rs937 delG/delG genotypes was detected in PSP, further extending the haplotype described previously. These results are consistent with the hypothesis that a change either in the 5′ or in the 3′ flanking regions of the tau gene, or even other genes contained in the H1E haplotype, could increase the genetic susceptibility to PSP. © 2002 Movement Disorder Society

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