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Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism

Abstract

Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.

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Figure 1: Expression of NLGN genes in the human brain.
Figure 2: Screening for mutations in NLGN3 and NLGN4 in autistic individuals.

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References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn. (American Psychiatric Press, Washington D.C., 1994).

  2. Gillberg, C. Br. J. Psychiatry 172, 200–209 (1998).

    Article  CAS  Google Scholar 

  3. Folstein, S.E. & Rosen-Sheidley, B. Nat. Rev. Genet. 2, 943–955 (2001).

    Article  CAS  Google Scholar 

  4. Gillberg, C. J. Autism Dev. Disord 28, 415–425 (1998).

    Article  CAS  Google Scholar 

  5. Thomas, N.S. et al. Hum. Genet. 104, 43–48 (1999).

    Article  CAS  Google Scholar 

  6. Shao, Y. et al. Am. J. Med. Genet. 114, 99–105 (2002).

    Article  Google Scholar 

  7. Auranen, M. et al. Am. J. Hum. Genet. 71, 777–390 (2002).

    Article  Google Scholar 

  8. Bolliger, M.F., Frei, K., Winterhalter, K.H. & Gloor, S.M. Biochem. J. 356, 581–588 (2001).

    Article  CAS  Google Scholar 

  9. Philibert, R.A., Winfield, S.L., Sandhu, H.K., Martin, B.M. & Ginns, E.I. Gene 246, 303–310 (2000).

    Article  CAS  Google Scholar 

  10. Ichtchenko, K., Nguyen, T. & Sudhof, T.C. J. Biol. Chem. 271, 2676–2682 (1996).

    Article  CAS  Google Scholar 

  11. Song, J.Y., Ichtchenko, K., Sudhof, T.C. & Brose, N. Proc. Natl. Acad. Sci. USA 96, 1100–1105 (1999).

    Article  CAS  Google Scholar 

  12. Scheiffele, P., Fan, J.H., Choih, J., Fetter, R. & Serafini, T. Cell 101, 657–669 (2000).

    Article  CAS  Google Scholar 

  13. Tsigelny, I., Shindyalov, I.N., Bourne, P.E., Sudhof, T.C. & Taylor, P. Protein Sci. 9, 180–185 (2000).

    Article  CAS  Google Scholar 

  14. Nguyen, T. & Sudhof, T.C. J. Biol. Chem. 272, 26032–26039 (1997).

    Article  CAS  Google Scholar 

  15. Jamain, S. et al. Mol. Psychiatry 7, 302–310 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the affected individuals and their families for agreeing to participate in this study, the délégation à la recherche clinique de l'assistance publique des hôpitaux de Paris for promoting this study, the Centre d'Investigations Cliniques de l'Hôpital Robert Debré for obtaining the blood samples from the French families, V. Sazdovitch for providing brain samples and C. Bouchier and S. Duthoy for use of the sequencing facilities at the Génopole Pasteur. This work was funded by the French Research Ministry (Actions Concertées Incitatives), the Institut National de la Santé et la Recherche Médicale, France Télécom and the Swedish Medical Research Council.

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Correspondence to Thomas Bourgeron.

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Jamain, S., Quach, H., Betancur, C. et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34, 27–29 (2003). https://doi.org/10.1038/ng1136

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