Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia
Abstract
We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.
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CHMP2B downregulation or expression of disease-associated CHMP2B mutants in Drosophila and mammalian cell lines results in aberrant endosomal structures, impaired autophagosome maturation, and cytosolic TARDBP aggregates.
“CHMP2B downregulation or expression of disease-associated CHMP2B mutants in Drosophila and mammalian cell lines results in aberrant endosomal structures, impaired autophagosome maturation, and cytosolic TARDBP aggregates [264,265,268,269].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [264]
CHMP2B mutations were initially associated with rare cases of chromosome 3-linked familial FTD.
“CHMP2B mutations were initially associated with rare cases of chromosome 3-linked familial FTD [264,265]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [264]
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- Authors
- Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sørensen, S. A., Gydesen, S., Fisher, E. M., & Collinge, J.
- Affiliations
- MRC Prion Unit (GB)
- Addenbrooke's Hospital (GB)
- University of Copenhagen (DK)
- MRC Cognition and Brain Sciences Unit (GB)
- University of Cambridge (GB)
- Dantherm Power (Denmark) (DK)
- Skåne University Hospital (SE)
- UCL Queen Square Institute of Neurology (GB)
- Copenhagen University Hospital (DK)
- Holbæk Sygehus (DK)
- Corresponding author
- Fisher, Elizabeth MC
- ORCID
- Venue
- Nature Genetics
- Published
- 2005-07-24
- Volume
- 37
- Issue
- 8
- Pages
- 806-808
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2034183549
- Cited by
- 822
- References
- 15
- Citations by year
- 2026: 17 · 2025: 29 · 2024: 20 · 2023: 31 · 2022: 29 · 2021: 35 · 2020: 37 · 2019: 32 · 2018: 37 · 2017: 35 · 2016: 46 · 2015: 42 · 2014: 27 · 2013: 33 · 2012: 58
- FWCI
- 33.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- frontotemporal dementia, CHMP2B, endosomal sorting, aberrant mRNA splicing, missense mutations, autosomal dominant inheritance, chromosome 3, neurodegeneration
- MeSH terms
- Dementia, Humans, Mutation, Nerve Tissue Proteins, Pedigree, RNA Splicing, Mutation, Missense, Endosomal Sorting Complexes Required for Transport
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