SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles
Open accessAbstract
Autism is a neurodevelopmental disorder characterized by impaired social reciprocity, impaired communication and stereotypical behaviors. Despite strong evidence for a genetic basis, few susceptibility genes have been identified. Here, we describe the positional cloning of SCAMP5, CLIC4 and PPCDC as candidate genes for autism, starting from a person with idiopathic, sporadic autism carrying a de novo chromosomal translocation. One of these genes, SCAMP5 is silenced on the derivative chromosome, and encodes a brain-enriched protein involved in membrane trafficking, similar to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold increase in stimulated secretion of large dense-core vesicles (LDCVs), while overexpression suppressed secretion. Moreover, ultrastructural analysis of blood platelets from the patients with haploinsufficieny of one of the three candidate genes, showed morphological abnormalities of dense-core granules, which closely resemble LDCVs. Taken together, this study shows that in three independent patients with autism three different negative regulators of LDCV secretion are affected, respectively, suggesting that in at least a subgroup of patients the regulation of neuronal vesicle trafficking may be involved in the pathogenesis of autism.
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The first three M12 hubs (A2BP1, APBA2, SCAMP5) have previously been implicated in autism.
“The first three of these genes have previously been implicated in autism 14-16”
From Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology (2011) · cites this paper as [15]
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Savelyeva, L., Sagulenko, E., Schmitt, J. G., & Schwab, M. (2005) · Cancer Letters · doi:10.1016/j.canlet.2005.08.033 · Cited by 20 · see citing works
Membrane Fusion: Caught in a Trap
Short, B., & Barr, F. A. (2004) · Current Biology · doi:10.1016/j.cub.2004.02.017 · Cited by 15 · see citing works
Corstens, G. J. H., van Boxtel, R., van den Hurk, M. J. J., et al. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01439.x · Cited by 7 · see citing works
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Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · see citing works
Casey, J. P., Magalhaes, T., Conroy, J. M., Regan, R., Shah, N., Anney, R., Shields, D. C., Abrahams, B. S., Almeida, J., Bacchelli, E., et al. (2012) · Human Genetics · doi:10.1007/s00439-011-1094-6 · Cited by 200 · see citing works
- Authors
- Castermans, D., Volders, K., Crepel, A., Backx, L., De Vos, R., Freson, K., Meulemans, S., Vermeesch, J. R., Schrander-Stumpel, C. T. R. M., De Rijk, P., Del-Favero, J., Van Geet, C., Van De Ven, W. J. M., Steyaert, J. G., Devriendt, K., & Creemers, J. W. M.
- Affiliations
- KU Leuven (BE)
- Center for Human Genetics (US)
- Maastricht University (NL)
- Vlaams Instituut voor Biotechnologie (BE)
- Corresponding author
- Creemers, John W.M.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-12
- Volume
- 19
- Issue
- 7
- Pages
- 1368-1378
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2144457054
- Cited by
- 100
- References
- 93
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 11 · 2012: 7
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Lirias (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- autism spectrum disorder, NBEA, CLIC4, positional cloning, haploinsufficiency, gene silencing, large dense core vesicles, vesicle secretion, membrane trafficking, dense core granules, platelet ultrastructure, candidate genes
- MeSH terms
- Adult, Animals, Autistic Disorder, Blood Platelets, Carrier Proteins, Cell Line, Chromosomes, Human, Pair 15, Humans, Male, Membrane Proteins, Nerve Tissue Proteins, Translocation, Genetic, Gene Silencing, Secretory Vesicles, Mice
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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