Cited by 822Alzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis ResearchCellular transport and secretion

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

Skibinski, Gaia, Parkinson, Nicholas J, Brown, Jeremy M, Chakrabarti, Lisa, Lloyd, Sarah L, Hummerich, Holger, Nielsen, Jørgen E, Hodges, John R +11 more·2005·Nature Genetics

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].”
  • 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]”

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  1. [6]Martin-Serrano, J., Yarovoy, A., Perez-Caballero, D. & Bieniasz, P.D. Proc. Natl. Acad. Sci. USA 100 , 12414-12419 (2003).

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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
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
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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