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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References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn. (American Psychiatric Press, Washington D.C., 1994).
Gillberg, C. Br. J. Psychiatry 172, 200–209 (1998).
Folstein, S.E. & Rosen-Sheidley, B. Nat. Rev. Genet. 2, 943–955 (2001).
Gillberg, C. J. Autism Dev. Disord 28, 415–425 (1998).
Thomas, N.S. et al. Hum. Genet. 104, 43–48 (1999).
Shao, Y. et al. Am. J. Med. Genet. 114, 99–105 (2002).
Auranen, M. et al. Am. J. Hum. Genet. 71, 777–390 (2002).
Bolliger, M.F., Frei, K., Winterhalter, K.H. & Gloor, S.M. Biochem. J. 356, 581–588 (2001).
Philibert, R.A., Winfield, S.L., Sandhu, H.K., Martin, B.M. & Ginns, E.I. Gene 246, 303–310 (2000).
Ichtchenko, K., Nguyen, T. & Sudhof, T.C. J. Biol. Chem. 271, 2676–2682 (1996).
Song, J.Y., Ichtchenko, K., Sudhof, T.C. & Brose, N. Proc. Natl. Acad. Sci. USA 96, 1100–1105 (1999).
Scheiffele, P., Fan, J.H., Choih, J., Fetter, R. & Serafini, T. Cell 101, 657–669 (2000).
Tsigelny, I., Shindyalov, I.N., Bourne, P.E., Sudhof, T.C. & Taylor, P. Protein Sci. 9, 180–185 (2000).
Nguyen, T. & Sudhof, T.C. J. Biol. Chem. 272, 26032–26039 (1997).
Jamain, S. et al. Mol. Psychiatry 7, 302–310 (2002).
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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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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DOI: https://doi.org/10.1038/ng1136
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