Format

Send to:

Choose Destination
See comment in PubMed Commons below
Arch Neurol. 2003 May;60(5):698-702.

Novel tau polymorphisms, tau haplotypes, and splicing in familial and sporadic frontotemporal dementia.

Author information

  • 1Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 9095, USA.

Abstract

BACKGROUND:

A subset of familial cases (FTDP-17) of frontotemporal dementia (FTD) are caused by mutations in the tau gene. The role of tau gene mutations and haplotypes in sporadic FTD and the functional consequences of tau polymorphisms are unknown.

OBJECTIVES:

To investigate (1) the frequency of known FTDP-17 mutations in familial and sporadic FTD and compare these results with previous studies; (2) whether the tau H1 haplotype is associated with FTD; and (3) the functional effect of intronic tau sequence variations.

PATIENTS AND METHODS:

Patients with familial and sporadic FTD were screened for mutations in the microtubule-binding region of tau. The frequencies of tau haplotypes and genotypes were compared between patients with FTD and control subjects. We analyzed the splicing effect of novel intronic polymorphisms associated with FTD.

RESULTS:

The P301L mutation was detected in 11% of familial FTD cases. The H1 haplotype was not overrepresented in patients with FTD, but the P301L mutation appeared on the background of the H2 tau haplotype. We identified 4 novel single nucleotide polymorphisms in intron 9 and a 9-base pair deletion in intron 4A. A C-to-T transition 177 base pairs upstream from exon 10 was significantly increased in patients with FTD compared with controls. Direct analysis of brain tissue from a patient with this variant showed an increase in exon 10-containing tau transcripts.

CONCLUSIONS:

Sequence variations in intronic or regulatory regions of tau may have previously unrecognized consequences leading to tau dysfunction and neurodegeneration.

PMID:
12756133
[PubMed - indexed for MEDLINE]
PMCID:
PMC2072863
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Write to the Help Desk