Molecular Genetics of Chromosome 17 Tauopathies
Abstract
A bstract: The identification of mutations in the gene encoding the micro‐tubule associated protein tau in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) demonstrated that tau dysfunction can lead to neurodegeneration. At least 11 missense mutations and 1 deletion mutation (ΔK280) have been identified in exons 9–13 that encode the microtubule binding domains of tau. In addition, five mutations have been found close to the 5′ splice site of exon 10. The different FTDP‐17 mutations have multiple effects on the biology and function of tau. These varied pathogenic mechanisms likely explain the wide range of clinical and neuropathological features observed in different families with FTDP‐17. In addition to the highly penetrant mutations that are found in large families with FTDP‐17, a common extended haplotype in the tau gene also appears to be a risk factor in the development of the apparently sporadic tauopathy, progressive supranuclear palsy (PSP). The mechanism by which this common variability in the tau gene influences the development of PSP is unclear; however, it further suggests a central role for tau in the pathogenesis of several neurodegenerative conditions including Alzheimer's disease (AD).
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Several tau mutations linked to FTDP-17 have been identified.
“Several tau mutations linked to FTDP-17 have been identified (2 -7)”
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Self-citationThe microtubule binding domain of tau protein
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- Authors
- HUTTON, M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- HUTTON, MICHAEL
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 920
- Issue
- 1
- Pages
- 63-73
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2091063187
- Cited by
- 92
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tauopathy, tau gene mutations, chromosome 17, progressive supranuclear palsy, tau protein, missense mutations, haplotypes, neurodegeneration, Alzheimer's disease, tau functions
- MeSH terms
- Chromosome Mapping, Chromosomes, Human, Pair 17, Dementia, Exons, Humans, Mutation, Parkinson Disease, Polymorphism, Genetic, Supranuclear Palsy, Progressive, tau Proteins, Mutation, Missense
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