Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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

Nature Genetics volume 37, pages 806–808 (2005)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Genomic and transcriptional defects of CHMP2B.
Figure 2: Overexpression of mutant CHMP2B isoforms produces an aberrant phenotype.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Knopman, D.S. et al. Neurology 40, 251–256 (1990).

    Article  CAS  Google Scholar 

  2. Hosler, B.A. et al. J. Am. Med. Assoc. 284, 1664–1669 (2000).

    Article  CAS  Google Scholar 

  3. Wilhelmsen, K.C. et al. Am. J. Hum. Genet. 55, 1159–1165 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Gydesen, S. et al. Neurology 59, 1585–1594 (2002).

    Article  CAS  Google Scholar 

  5. Yancopoulou, D. et al. J. Neuropathol. Exp. Neurol. 62, 878–882 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Babst, M. et al. Dev. Cell 3, 271–282 (2002).

    Article  CAS  Google Scholar 

  8. Katzmann, D.J. et al. Cell 106, 145–155 (2001).

    Article  CAS  Google Scholar 

  9. Babst, M. et al. EMBO J. 17, 2982–2993 (1998).

    Article  CAS  Google Scholar 

  10. Harrison, R.E. et al. Mol. Cell. Biol. 23, 6494–6506 (2003).

    Article  CAS  Google Scholar 

  11. Fukuda, M. J. Biol. Chem. 266, 21327–21330 (1991).

    CAS  PubMed  Google Scholar 

  12. Kunita, R. et al. J. Biol. Chem. 279, 38626–38635 (2004).

    Article  CAS  Google Scholar 

  13. Reid, E. et al. Hum. Mol. Genet. 14, 19–38 (2005).

    Article  CAS  Google Scholar 

  14. Nixon, R.A. Neurobiol. Aging 26, 373–382 (2005).

    Article  CAS  Google Scholar 

  15. Collinge, J. et al. J. Neurol. Neurosurg. Psychiatry 57, 762–768 (1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all members of the Danish family for their support of this research; J. Hardy for his early contribution to research on this kindred; G. Schiavo, G. Banting, J. Linehan, C. Powel, P. Jat, A. Clarke and E. Englund for their assistance with these studies; and R. Young for graphics. This work was funded by the UK Medical Research Council.

Author information

Author notes

  1. Lisa Chakrabarti

    Present address: Department of Laboratory Medicine, University of Washington Medical Center, Seattle, Washington, USA

Authors and Affiliations

  1. MRC Prion Unit, Institute of Neurology, University College London, London, UK

    Gaia Skibinski, Nicholas J Parkinson, Lisa Chakrabarti, Sarah L Lloyd, Holger Hummerich, Sebastian Brandner & John Collinge

  2. Department of Neurology, Addenbrooke's Hospital, Cambridge, UK

    Jeremy M Brown

  3. Department of Medical Biochemistry and Genetics, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Denmark

    Jørgen E Nielsen & Sven Asger Sørensen

  4. Memory Disorders Research Unit, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Jørgen E Nielsen, Anders Gade & Peter Johannsen

  5. Department of Neurology, MRC Cognition and Brain Sciences Unit, Addenbrooke's Hospital, Cambridge, UK

    John R Hodges

  6. Department of Clinical Neurosciences, Centre for Brain Repair, Cambridge University, Cambridge, UK

    Maria Grazia Spillantini

  7. Parkvaenget Nursing Home, Holstebro, Denmark

    Tove Thusgaard

  8. Department of Neurodegenerative Disease, Institute of Neurology, University College, London, UK

    Sebastian Brandner, Martin N Rossor, Elizabeth MC Fisher & John Collinge

  9. Department of Pathology, University Hospital of Lund, Lund, Sweden

    Arne Brun

  10. Department of Psychology, University of Copenhagen, Rigshospitalet, Denmark

    Anders Gade

  11. Department of Psychiatry, Central Hospital, Holbaek, Denmark

    Susanne Gydesen

Authors
  1. Gaia Skibinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicholas J Parkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeremy M Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lisa Chakrabarti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sarah L Lloyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Holger Hummerich
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jørgen E Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. John R Hodges
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria Grazia Spillantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tove Thusgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sebastian Brandner
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Arne Brun
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Martin N Rossor
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Anders Gade
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Peter Johannsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sven Asger Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Susanne Gydesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Elizabeth MC Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. John Collinge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth MC Fisher.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

The Danish pedigree showing generations 1 to 3. (PDF 337 kb)

Supplementary Fig. 2

Inheritance of the disease haplotype in the Danish pedigree in branches taken from generations 1 to 3. (PDF 64 kb)

Supplementary Fig. 3

Electropherograms of the mutations identified in CHMP2b. (PDF 327 kb)

Supplementary Fig. 4

Multiple protein alignment of human CHMP2b, mutant isoforms and orthologs. (PDF 128 kb)

Supplementary Fig. 5

Overexpression of CHMP2bΔ10 displays an aberrant phenotype in undifferentiated PC12 cells. (PDF 393 kb)

Supplementary Table 1

Primer sequences for CHMP2b. (PDF 27 kb)

Supplementary Methods (PDF 64 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Skibinski, G., Parkinson, N., Brown, J. et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet 37, 806–808 (2005). https://doi.org/10.1038/ng1609

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1609

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing