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Title: SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles
Authors: Castermans, Dries
Volders, Karolien
Crepel, An
Backx, Liesbeth
De Vos, Rita
Freson, Kathleen
Meulemans, Sandra
Vermeesch, Joris
Schrander-Stumpel, Connie T R M
De Rijk, Peter
Del-Favero, Jurgen
Van Geet, Christel
Van de Ven, Willem
Steyaert, Jean
Devriendt, Koenraad
Creemers, John # ×
Issue Date: Jan-2010
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:19 issue:7 pages:1368-1378
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, similarly to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a twofold 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 (DCGs), 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.
URI: 
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Molecular Cell Biology (-)
Laboratory for Biochemical Neuroendocrinology
Laboratory for Genetics of Human Development
Clinical Genetics
Translational Cell & Tissue Research
Molecular and Vascular Biology
Research Group Psychiatry
× corresponding author
# (joint) last author

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