title: The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronic variant of the disease-associated H1 haplotype in Italian cases.
abstract: Mutations in coding exons or exon 10 5'-splice-site of the gene for microtubule-associated protein tau can cause chromosome 17-linked frontotemporal dementia and parkinsonism (FTDP-17). We sequenced the 11 coding exons plus exon-intron boundaries of the tau gene in 15 cases of progressive supranuclear palsy (PSP), and found no mutations in coding exons or exon ten 5'-splice sites. These data indicate that typical PSP is not associated with tau gene mutations similar to those causing FTDP-17. We also observed a +39deltaG base change in the intron following exon 4 in three out of 69 PSP cases (all three Italians), whereas it was not found in 150 Dutch controls and once in 112 Italian controls. The +39deltaG variant arose in the context of the PSP-associated tau H1 haplotype. Although a pathogenic role cannot be entirely excluded, +39deltaG is likely to be a rare polymorphism that may be in linkage disequilibrium with a biologically relevant locus inside or near to the tau gene.
authors.affiliation: Department of Neurosciences, La Sapienza University, Roma, Italy. bonifati@uniroma1.it
authors.forename: V
authors.initials: V
authors.lastname: Bonifati
authors.forename: M
authors.initials: M
authors.lastname: Joosse
authors.forename: D J
authors.initials: DJ
authors.lastname: Nicholl
authors.forename: N
authors.initials: N
authors.lastname: Vanacore
authors.forename: P
authors.initials: P
authors.lastname: Bennett
authors.forename: P
authors.initials: P
authors.lastname: Rizzu
authors.forename: G
authors.initials: G
authors.lastname: Fabbrini
authors.forename: R
authors.initials: R
authors.lastname: Marconi
authors.forename: C
authors.initials: C
authors.lastname: Colosimo
authors.forename: N
authors.initials: N
authors.lastname: Locuratolo
authors.forename: F
authors.initials: F
authors.lastname: Stocchi
authors.forename: U
authors.initials: U
authors.lastname: Bonuccelli
authors.forename: M
authors.initials: M
authors.lastname: De Mari
authors.forename: G
authors.initials: G
authors.lastname: Wenning
authors.forename: P
authors.initials: P
authors.lastname: Vieregge
authors.forename: B
authors.initials: B
authors.lastname: Oostra
authors.forename: G
authors.initials: G
authors.lastname: Meco
authors.forename: P
authors.initials: P
authors.lastname: Heutink
mesh_terms: D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy; D009154:Mutation / Q000235:genetics*; D020033:Protein Isoforms; D012326:RNA Splicing / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins