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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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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The first mutations identified in idiopathic autism involve synaptic genes like NLGN3 and NLGN4X, or SHANK3.
“the first mutations identified in idiopathic autism involve synaptic genes like NLGN3 and NLGN4X,27,28 or SHANK329-31”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [28]
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Hunter, J. W., Mullen, G. P., McManus, J. R., Heatherly, J. M., Duke, A., & Rand, J. B. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.003442 · Cited by 86 · see citing works
Modeling autism-relevant behavioral phenotypes in rats and mice: Do ‘autistic’ rodents exist?
Servadio, M., Vanderschuren, L. J. M. J., & Trezza, V. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000163 · Cited by 76 · see citing works
Genome-wide association study meta-analysis of suicide death and suicidal behavior
Li, Q. S., Shabalin, A. A., DiBlasi, E., Gopal, S., Canuso, C. M., FinnGen, I. S. G. C., Palotie, A., Drevets, W. C., Docherty, A. R., & Coon, H. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01828-9 · Cited by 68 · see citing works
Hammer, M., Krueger-Burg, D., Tuffy, L. P., Cooper, B. H., Taschenberger, H., Goswami, S. P., Ehrenreich, H., Jonas, P., Varoqueaux, F., Rhee, J.-S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.011 · Cited by 66 · see citing works
Chanda, S., Aoto, J., Lee, S.-J., Wernig, M., & Südhof, T. C. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.20 · Cited by 60 · see citing works
Matuszek, G., & Talebizadeh, Z. (2009) · BMC Medical Genetics · doi:10.1186/1471-2350-10-102 · Cited by 48 · see citing works
A new synaptic player leading to autism risk: Met receptor tyrosine kinase
Judson, M. C., Eagleson, K. L., & Levitt, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9081-8 · Cited by 43 · see citing works
Bonnet-Brilhault, F., Alirol, S., Blanc, R., Bazaud, S., Marouillat, S., Thépault, R.-A., Andres, C. R., Lemonnier, É., Barthélémy, C., Raynaud, M., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.75 · Cited by 41 · see citing works
Self-citationThe autism diagnosis in translation: shared affect in children and mouse models of ASD
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Cellot, G., & Cherubini, E. (2014) · Physiological Reports · doi:10.14814/phy2.12077 · Cited by 38 · see citing works
Developing new pharmacotherapies for autism
Ecker, C., Spooren, W., & Murphy, D. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12113 · Cited by 31 · see citing works
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Autism spectrum disorders associated with X chromosome markers in French-Canadian males
Gauthier, J., Joober, R., Dubé, M.-P., St-Onge, J., Bonnel, A., Gariépy, D., Laurent, S., Najafee, R., Lacasse, H., St-Charles, L., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001756 · Cited by 23 · see citing works
- 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
- ORCID
- 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)
- PMC
- PMC1182268
- 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
- bronze
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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