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.

Another piece of the autism puzzle

Nature Genetics volume 42, pages 478–479 (2010)Cite this article

Subjects

A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability.

Autism is an often-devastating neurodevelopmental disorder characterized by impairments in social communication and language development, accompanied by highly restricted interests and/or repetitive stereotyped behaviors. It is the prototype of a continuum of syndromes referred to as autism-spectrum disorders (ASD) that have a prevalence of approximately 1% in the general population. Despite strong evidence for a genetic contribution, the identification of genetic variants contributing to ASD susceptibility has proven elusive, owing in part to a high degree of allelic and locus heterogeneity. However, recent discoveries from studies that have identified rare genetic variation in individuals with ASD, together with findings from investigations of Mendelian mental retardation syndromes, are beginning to illuminate molecular and cellular mechanisms of disease. On page 489 of this issue, Gudrun Rappold and colleagues1 report the discovery of rare de novo, apparently loss-of-function mutations in SHANK2 in individuals with ASD, mental retardation or both.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Molecular network at the synapse includes molecules implicated in social disability.

References

  1. Berkel, S. et al. Nat. Genet. 42, 489–491 (2010).

    Article  CAS  Google Scholar 

  2. Jamain, S. et al. Nat. Genet. 34, 27–29 (2003).

    Article  CAS  Google Scholar 

  3. Laumonnier, F. et al. Am. J. Hum. Genet. 74, 552–557 (2004).

    Article  CAS  Google Scholar 

  4. Bill, B.R. & Geschwind, D.H. Curr. Opin. Genet. Dev. 19, 271–278 (2009).

    Article  CAS  Google Scholar 

  5. Varoqueaux, F. et al. Neuron 51, 741–754 (2006).

    Article  CAS  Google Scholar 

  6. Graf, E.R., Zhang, X., Jin, S.X., Linhoff, M.W. & Craig, A.M. Cell 119, 1013–1026 (2004).

    Article  CAS  Google Scholar 

  7. Chih, B., Engelman, H. & Scheiffele, P. Science 307, 1324–1328 (2005).

    Article  CAS  Google Scholar 

  8. Gauthier, J. et al. Proc. Natl. Acad. Sci. USA 107, 7863–7868 (2010).

    Article  CAS  Google Scholar 

  9. Sebat, J., Levy, D.L. & McCarthy, S.E. Trends Genet. 25, 528–535 (2009).

    Article  CAS  Google Scholar 

  10. Bear, M.F., Huber, K.M. & Warren, S.T. Trends Neurosci. 27, 370–377 (2004).

    Article  CAS  Google Scholar 

  11. McBride, S.M. et al. Neuron 45, 753–764 (2005).

    Article  CAS  Google Scholar 

  12. Dölen, G. et al. Neuron 56, 955–962 (2007).

    Article  Google Scholar 

  13. Goffin, A., Hoefsloot, L.H., Bosgoed, E., Swillen, A. & Fryns, J.P. Am. J. Med. Genet. 105, 521–524 (2001).

    Article  CAS  Google Scholar 

  14. Zhou, J. et al. J. Neurosci. 29, 1773–1783 (2009).

    Article  CAS  Google Scholar 

  15. Ehninger, D. et al. Nat. Med. 14, 843–848 (2008).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Child Psychiatry, Matthew W. State is at the Program on Neurogenetics and the, Psychiatry and Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.,

    Matthew W State

Authors
  1. Matthew W State
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew W State.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

State, M. Another piece of the autism puzzle. Nat Genet 42, 478–479 (2010). https://doi.org/10.1038/ng0610-478

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0610-478

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