Autism-associated 16p11.2 microdeletion impairs prefrontal functional connectivity in mouse and human
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Human genetic studies are rapidly identifying variants that increase risk for neurodevelopmental disorders. However, it remains unclear how specific mutations impact brain function and contribute to neuropsychiatric risk. Chromosome 16p11.2 deletion is one of the most common copy number variations in autism and related neurodevelopmental disorders. Using resting state functional MRI data from the Simons Variation in Individuals Project (VIP) database, we show that 16p11.2 deletion carriers exhibit impaired prefrontal connectivity, resulting in weaker long-range functional coupling with temporal-parietal regions. These functional changes are associated with socio-cognitive impairments. We also document that a mouse with the same genetic deficiency exhibits similarly diminished prefrontal connectivity, together with thalamo-prefrontal miswiring and reduced long-range functional synchronization. These results reveal a mechanistic link between specific genetic risk for neurodevelopmental disorders and long-range functional coupling, and suggest that deletion in 16p11.2 may lead to impaired socio-cognitive function via dysregulation of prefrontal connectivity.
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Humans and mice with 16p11.2 deletions both show reduced prefrontal cortical connectivity.
“Both humans and mice carrying 16p11.2 deletions display reduced prefrontal cortical connectivity [100]”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [100]
Prefrontal cortex disruption contributes to 16p11.2 CNV phenotypes.
“further suggesting a role for PFC disruption in 16p11.2 CNVs.”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [100]
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- Authors
- Bertero, A., Liska, A., Pagani, M., Parolisi, R., Masferrer, M. E., Gritti, M., Pedrazzoli, M., Galbusera, A., Sarica, A., Cerasa, A., Buffelli, M., Tonini, R., Buffo, A., Gross, C., Pasqualetti, M., & Gozzi, A.
- Affiliations
- University of Pisa (IT)
- Italian Institute of Technology (IT)
- Neuroscience Institute Cavalieri Ottolenghi (IT)
- European Molecular Biology Laboratory (IT)
- National Research Council (IT)
- Istituto S.Anna Crotone (IT)
- University of Verona (IT)
- Corresponding author
- Gozzi, Alessandro
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-05-02
- Volume
- 141
- Issue
- 7
- Pages
- 2055-2065
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2801166051
- Cited by
- 120
- References
- 82
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 13 · 2023: 11 · 2022: 17 · 2021: 15 · 2020: 19 · 2019: 16 · 2018: 6
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, other-oa)
- Funders
- Simons Foundation (SFARI 314688, 400101)
- Brain and Behavior Foundation (2017 NARSAD)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- 16p11.2 microdeletion, autism spectrum disorder, copy number variation, prefrontal cortex, long-range functional connectivity, resting-state fMRI, mouse model, neurodevelopmental disorders, genetic risk
- MeSH terms
- Adolescent, Animals, Autistic Disorder, Child, Chromosome Deletion, Chromosomes, Human, Pair 16, Cognition, Disease Models, Animal, Female, Humans, Magnetic Resonance Imaging, Male, Membrane Potentials, Intellectual Disability, Nerve Net, Temporal Lobe, Prefrontal Cortex, Mice, Knockout, Chromosome Disorders, Mice, DNA Copy Number Variations, Cognitive Dysfunction, Neurodevelopmental Disorders
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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