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.

A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

Nature Neuroscience volume 7, pages 1187–1189 (2004)Cite this article

Abstract

An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1: Identification of a de novo mutation in TrkB.
Figure 2: Phenotype of 8-year-old boy with the Y722C mutant TrkB.

References

  1. Kernie, S.G., Liebl, D.J. & Parada, L.F. EMBO J. 19, 1290–1300 (2000).

    Article  CAS  Google Scholar 

  2. Xu, B. et al. Nat. Neurosci. 6, 736–742 (2003).

    Article  CAS  Google Scholar 

  3. Rios, M. et al. Mol. Endocrinol. 15, 1748–1757 (2001).

    Article  CAS  Google Scholar 

  4. Huang, E.J. & Reichardt, L.F. Annu. Rev. Neurosci. 24, 677–736 (2001).

    Article  CAS  Google Scholar 

  5. O'Rahilly, S., Farooqi, I.S., Yeo, G.S. & Challis, B.G. Endocrinology 144, 3757–3764 (2003).

    Article  CAS  Google Scholar 

  6. Ultsch, M.H. et al. J. Mol. Biol. 290, 149–159 (1999).

    Article  CAS  Google Scholar 

  7. Guiton, M., Gunn-Moore, F.J., Stitt, T.N., Yancopoulos, G.D. & Tavare, J.M. J. Biol. Chem. 269, 30370–30377 (1994).

    CAS  PubMed  Google Scholar 

  8. McCarty, J.H. & Feinstein, S.C. Oncogene 16, 1691–1700 (1998).

    Article  CAS  Google Scholar 

  9. Farooqi, I.S. et al. N. Engl. J. Med. 348, 1085–1095 (2003).

    Article  CAS  Google Scholar 

  10. Erickson, J.T. et al. J. Neurosci. 16, 5361–5371 (1996).

    Article  CAS  Google Scholar 

  11. Donovan, M.J. et al. Development 127, 4531–4540 (2000).

    CAS  Google Scholar 

  12. Elliot, C.D., Smith, P. & McCulloch, K. British Ability Scales II: Administration and Scoring Manual (NFER-Nelson Publishing Company Ltd, Windsor, UK, 1996).

    Google Scholar 

  13. Egan, M.F. et al. Cell 112, 257–269 (2003).

    Article  CAS  Google Scholar 

  14. Klein, R. et al. Cell 75, 113–122 (1993).

    Article  CAS  Google Scholar 

  15. Indo, Y. et al. Nat. Genet. 13, 485–488 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Wellcome Trust (G.S.H.Y., I.S.F., J.R. and S.O.R.) and the Medical Research Council (J.G., J.K. and S.O.R.). We are indebted to the patients and their families for their participation and to the physicians involved in the Genetics of Obesity Study (GOOS).

Author information

Author notes

  1. Giles S H Yeo and Chiao-Chien Connie Hung: These authors contributed equally to this work.

Authors and Affiliations

  1. University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK

    Giles S H Yeo, Chiao-Chien Connie Hung, Justin Rochford, Julia Keogh, Juliette Gray, Stephen O'Rahilly & I Sadaf Farooqi

  2. Castleford and Normanton District Hospital, Castleford, WF10 5LT, Yorkshire, UK

    Shoba Sivaramakrishnan

Authors
  1. Giles S H Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiao-Chien Connie Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Justin Rochford
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julia Keogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliette Gray
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shoba Sivaramakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen O'Rahilly
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I Sadaf Farooqi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen O'Rahilly.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yeo, G., Connie Hung, CC., Rochford, J. et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 7, 1187–1189 (2004). https://doi.org/10.1038/nn1336

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1336

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