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.
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.
Bonifati
V
V
Department of Neurosciences, La Sapienza University, Roma, Italy. bonifati@uniroma1.it
Joosse
M
M
Nicholl
D J
DJ
Vanacore
N
N
Bennett
P
P
Rizzu
P
P
Fabbrini
G
G
Marconi
R
R
Colosimo
C
C
Locuratolo
N
N
Stocchi
F
F
Bonuccelli
U
U
De Mari
M
M
Wenning
G
G
Vieregge
P
P
Oostra
B
B
Meco
G
G
Heutink
P
P
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*
D020033:Protein Isoforms; D016875:tau Proteins