Tau gene mutation in familial progressive subcortical gliosis

M. Goedert, M. G. Spillantini, R. A. Crowther, S. G. Chen, P. Parchi, M. Tabaton, D. J. Lanska, W. R. Markesbery, K. C. Wilhelmsen, Dennis W Dickson, R. B. Petersen, P. Gambetti

Research output: Contribution to journalArticle

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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 (refs. 1-3). 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.

Original languageEnglish (US)
Pages (from-to)454-457
Number of pages4
JournalNature Medicine
Volume5
Issue number4
DOIs
StatePublished - Apr 1999

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Gliosis
Genes
Chromosomes
Mutation
Dementia
Frontotemporal Dementia
Pathology
Introns
Exons
Protein Isoforms
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 17
Genetic Linkage
Parkinsonian Disorders
Neuroglia
Hereditary Diffuse Leukoencephalopathy with Spheroids
Alzheimer Disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Goedert, M., Spillantini, M. G., Crowther, R. A., Chen, S. G., Parchi, P., Tabaton, M., ... Gambetti, P. (1999). Tau gene mutation in familial progressive subcortical gliosis. Nature Medicine, 5(4), 454-457. https://doi.org/10.1038/7454

Tau gene mutation in familial progressive subcortical gliosis. / Goedert, M.; Spillantini, M. G.; Crowther, R. A.; Chen, S. G.; Parchi, P.; Tabaton, M.; Lanska, D. J.; Markesbery, W. R.; Wilhelmsen, K. C.; Dickson, Dennis W; Petersen, R. B.; Gambetti, P.

In: Nature Medicine, Vol. 5, No. 4, 04.1999, p. 454-457.

Research output: Contribution to journalArticle

Goedert, M, Spillantini, MG, Crowther, RA, Chen, SG, Parchi, P, Tabaton, M, Lanska, DJ, Markesbery, WR, Wilhelmsen, KC, Dickson, DW, Petersen, RB & Gambetti, P 1999, 'Tau gene mutation in familial progressive subcortical gliosis', Nature Medicine, vol. 5, no. 4, pp. 454-457. https://doi.org/10.1038/7454
Goedert M, Spillantini MG, Crowther RA, Chen SG, Parchi P, Tabaton M et al. Tau gene mutation in familial progressive subcortical gliosis. Nature Medicine. 1999 Apr;5(4):454-457. https://doi.org/10.1038/7454
Goedert, M. ; Spillantini, M. G. ; Crowther, R. A. ; Chen, S. G. ; Parchi, P. ; Tabaton, M. ; Lanska, D. J. ; Markesbery, W. R. ; Wilhelmsen, K. C. ; Dickson, Dennis W ; Petersen, R. B. ; Gambetti, P. / Tau gene mutation in familial progressive subcortical gliosis. In: Nature Medicine. 1999 ; Vol. 5, No. 4. pp. 454-457.
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