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

Dries Castermans, Karolien Volders, An Crepel, Liesbeth Backx, Rita De Vos, Kathleen Freson, Sandra Meulemans, Joris Robert Vermeesch, Connie T. R. M. Schrander-Stumpel, Peter De Rijk, Jurgen Del Favero, Chris van Geet, Wim J. M. Van De Ven, Jean G. Steyaert, Koen Devriendt, John W. M. Creemers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)1368-1378
JournalHuman Molecular Genetics
Issue number7
Publication statusPublished - Apr 2010

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