title: Tau gene mutation in familial progressive subcortical gliosis.
abstract: Familial forms of frontotemporal dementias are associated with mutations in the tau gene. A kindred affected by progressive subcortical gliosis (PSG), a rare form of presenile dementia, has genetic linkage to chromosome 17q21-22. This kindred (PSG-1) is included in the 'frontotemporal dementias and Parkinsonism linked to chromosome 17' group along with kindreds affected by apparently different forms of atypical dementias. Some of these kindreds have mutations in the tau gene. We report here that PSG-1 has a tau mutation at position +16 of the intron after exon 10. The mutation destabilizes a predicted stem-loop structure and leads to an over-representation of the soluble four-repeat tau isoforms, which assemble into wide, twisted, ribbon-like filaments and ultimately result in abundant neuronal and glial tau pathology. The mutations associated with PSG and other atypical dementias can be subdivided into three groups according to their tau gene locations and effects on tau. The existence of tau mutations with distinct pathogenetic mechanisms may explain the phenotypic heterogeneity of atypical dementias that previously led to their classification into separate disease entities.
authors: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors: M
authors: M
authors: Goedert
authors: M G
authors: MG
authors: Spillantini
authors: R A
authors: RA
authors: Crowther
authors: S G
authors: SG
authors: Chen
authors: P
authors: P
authors: Parchi
authors: M
authors: M
authors: Tabaton
authors: D J
authors: DJ
authors: Lanska
authors: W R
authors: WR
authors: Markesbery
authors: K C
authors: KC
authors: Wilhelmsen
authors: D W
authors: DW
authors: Dickson
authors: R B
authors: RB
authors: Petersen
authors: P
authors: P
authors: Gambetti
mesh_terms: D002540:Cerebral Cortex / Q000473:pathology*; D003704:Dementia / Q000235:genetics*; D005625:Frontal Lobe / Q000473:pathology; D005911:Gliosis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins