Cited by 768Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchNeuroscience and Neuropharmacology Research

X-Linked Mental Retardation and Autism Are Associated with a Mutation in the NLGN4 Gene, a Member of the Neuroligin Family

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Laumonnier, Frédéric, Bonnet-Brilhault, Frédérique, Gomot, Marie, Blanc, Romuald, David, Albert, Moizard, Marie-Pierre, Raynaud, Martine, Ronce, Nathalie +11 more·2004·The American Journal of Human Genetics

Abstract

A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.

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Crossref · 10.1086/382137

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Authors
Laumonnier, F., Bonnet-Brilhault, F., Gomot, M., Blanc, R., David, A., Moizard, M.-P., Raynaud, M., Ronce, N., Lemonnier, E., Calvas, P., Laudier, B., Chelly, J., Fryns, J.-P., Ropers, H.-H., Hamel, B. C. J., Andres, C., Barthélémy, C., Moraine, C., & Briault, S.
Affiliations
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Hôpital Purpan (FR)
  • Max Planck Institute for Molecular Genetics (DE)
Corresponding author
Briault, Sylvain
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2004-03
Volume
74
Issue
3
Pages
552-557
ISSN
0002-9297 (ISSN-L)
OpenAlex
W1996092810
Cited by
768
References
28
Citations by year
2026: 3 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 25 · 2021: 19 · 2020: 22 · 2019: 17 · 2018: 17 · 2017: 37 · 2016: 28 · 2015: 45 · 2014: 49 · 2013: 49 · 2012: 55
FWCI
23.31
Type
journal article
Language
en
Open access
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion, cc-by)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Fondation de France
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
neuroligin 4, X-linked intellectual disability, autism spectrum disorder, pervasive developmental disorders, premature stop codon, synaptogenesis, excitatory synapses, cognitive development, family studies
MeSH terms
Adolescent, Adult, Autistic Disorder, Carrier Proteins, Child, Child, Preschool, Female, Humans, Genetic Linkage, Male, Membrane Proteins, Mutation, Pedigree, Cell Adhesion Molecules, Neuronal, X-Linked Intellectual Disability

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