Sequencing of the tau gene in progressive supranuclear palsy reveals no missense or exon 10 splice-site mutations

V. Bonifati, N. Vanacore, D. Nicholl, N. Locuratolo, G. Fabbrini, R. Marconi, C. Colosimo, P. Vieregge, P. Bennett, G. Meco, P. Heutink

Research output: Contribution to journalArticlepeer-review


Different, independent studies have demonstrated an association between a polymorphic dinucleotide marker, found between exon 9 and exon 10 of the tau gene, and progressive supranuclear palsy (PSP). Several mutations in tau gene have recently been identified in families with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). In particular, some missense mutations in exon 10 or its 5'-splice-site induce disregulation of splicing, with excessive production of tau isoforms containing 4 microtubule-binding repeats (4R tau). The alteration of the normal balance of 4R versus 3R tau is therefore critical for tangles (NFT) formation and neurodegeneration. Since NFTs in PSP also consist of 4R tau isoforms we searched for pathogenic mutations in the tau gene in a series of clinically diagnosed PSP cases enrolled at several centers participating to the European Study Group on Atypical Parkinsonism Consortium (ESGAP). Fifteen PSP cases were selected for sequencing of the tau gene. Four of them had a positive family history of parkinsonism. All 11 coding exons of the tau gene including intron-exon boundaries were tested by direct sequence analysis using an ABI377 automatic sequencer and BigDye chemistry. Missense or exon 10 splice-site mutations were not detected. Some sequence alterations were identified, but they were also present in healthy controls. These findings suggest that PSP is not caused by tau gene mutations similar to those found in FTDP-17. Further molecular genetic studies are in progress.

Original languageEnglish
Pages (from-to)272
Number of pages1
JournalItalian Journal of Neurological Sciences
Issue number4
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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