The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronicvariant of the disease-associated H1 haplotype in Italian cases

Mutations in coding exons or exon 10 5'-splice-site of the gene for microtu bule-associated protein tau can cause chromosome 17-linked frontotemporal d ementia and parkinsonism (FTDP-17). We sequenced the 11 coding exons plus e xon-intron boundaries of the tau gene in 15 cases of progressive supranucle ar palsy (PSP), and found no mutations in coding exons or exon ten 5'-splic e sites. These data indicate that typical PSP is not associated with tau ge ne mutations similar to those causing FTDP-17. We also observed a +39 Delta G base change in the intron following exon 4 in th ree out of 69 PSP cases (all three Italians), whereas it was not found in 150 Dutch controls and o nce in 112 Italian controls. The +39 Delta G variant arose in the context o f the PSP-associated tau H1 haplotype. Although a pathogenic role cannot be entirely excluded, +39 Delta G is likely to be a rare polymorphism that ma y be in linkage disequilibrium with a biologically relevant locus inside or near to the tau gene. (C) 1999 Elsevier Science Ireland Ltd. All rights re served.