Cited by 100Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersCellular transport and secretion

SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles

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Castermans, Dries, Volders, Karolien, Crepel, An, Backx, Liesbeth, De Vos, Rita, Freson, Kathleen, Meulemans, Sandra, Vermeesch, Joris R. +8 more·2010·Human Molecular Genetics

Abstract

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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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
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
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

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