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

Nature Genetics volume 34, pages 27–29 (2003)Cite this article

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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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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Authors and Affiliations

  1. Laboratoire de Génétique Humaine et Fonctions Cognitives, Université Paris 7, Institut National de la Santé et la Recherche Médicale E0021, Institut Pasteur, Paris, 75015, France

    Stéphane Jamain, Hélène Quach & Thomas Bourgeron

  2. Institut National de la Santé et la Recherche Médicale U513, Faculté de Médecine, Université Paris XII, Créteil, 94000, France

    Catalina Betancur, Catherine Colineaux, Bruno Giros & Marion Leboyer

  3. Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg, 41119, Sweden

    Maria Råstam, I. Carina Gillberg, Henrik Soderstrom & Christopher Gillberg

  4. Department of Child and Adolescent Psychiatry, Hôpital Robert Debré, Paris, 75019, France

    Catherine Colineaux

  5. Department of Psychiatry, Hôpital Albert Chenevier et Henri Mondor, Créteil, 94000, France

    Marion Leboyer

  6. Saint George's Hospital Medical School, London, SW17 ORE, UK

    Christopher Gillberg

  7. Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg, Sweden

    Christopher Gillberg, Maria Råstam, Carina Gillberg, Agneta Nydén & Henrik Söderström

  8. Department of Psychiatry, Hôpital Albert Chenevier et Henri Mondor, Créteil, France

    Marion Leboyer

  9. Institut National de la Santé et la Recherche Médicale U513, Faculté de Médecine, Créteil, France

    Catalina Betancur, Anne Philippe & Bruno Giros

  10. Service de Psychopathologie de l'Enfant et l'Adolescent, Hôpital Robert Debré, Paris, France

    Catherine Colineaux, Deborah Cohen, Nadia Chabane & Marie-Christine Mouren-Siméoni

  11. Institut National de la Santé et la Recherche Médicale U289, Hôpital de la Salpêtrière, Paris, France

    Alexis Brice

  12. Centre for Child and Adolescent Psychiatry, University of Oslo, Oslo, Norway

    Eili Sponheim & Ingrid Spurkland

  13. Department of Pediatrics, Rikshospitalet, University of Oslo, Oslo, Norway

    Ola H. Skjeldal

  14. Department of Pediatrics, Georgetown University School of Medicine, Washington, D.C., USA

    Mary Coleman

  15. Children's National Medical Center, George Washington University School of Medicine, Washington, D.C., USA

    Philip L. Pearl

  16. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA

    Ira L. Cohen & John Tsiouris

  17. Divisione di Neuropsichiatria Infantile, Azienda Ospedaliera Senese, Siena, Italy

    Michele Zappella, Grazia Menchetti & Alfonso Pompella

  18. Department of General Psychiatry, University Hospital, Vienna, Austria

    Harald Aschauer

  19. Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gerpinnes, Loverval, Belgium

    Lionel Van Maldergem

Authors
  1. Stéphane Jamain
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  2. Hélène Quach
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  3. Catalina Betancur
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  4. Maria Råstam
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  5. Catherine Colineaux
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  6. I. Carina Gillberg
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  7. Henrik Soderstrom
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  8. Bruno Giros
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  9. Marion Leboyer
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  10. Christopher Gillberg
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  11. Thomas Bourgeron
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Consortia

Paris Autism Research International Sibpair Study

  • Christopher Gillberg
  • , Maria Råstam
  • , Carina Gillberg
  • , Agneta Nydén
  • , Henrik Söderström
  • , Marion Leboyer
  • , Catalina Betancur
  • , Anne Philippe
  • , Bruno Giros
  • , Catherine Colineaux
  • , Deborah Cohen
  • , Nadia Chabane
  • , Marie-Christine Mouren-Siméoni
  • , Alexis Brice
  • , Eili Sponheim
  • , Ingrid Spurkland
  • , Ola H. Skjeldal
  • , Mary Coleman
  • , Philip L. Pearl
  • , Ira L. Cohen
  • , John Tsiouris
  • , Michele Zappella
  • , Grazia Menchetti
  • , Alfonso Pompella
  • , Harald Aschauer
  •  & Lionel Van Maldergem

Corresponding author

Correspondence to Thomas Bourgeron.

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The authors declare no competing financial interests.

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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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