Autism spectrum disorder (ASD) is a condition defined by deficits in social interaction, communication, and selected behaviors and may affect up to 1.5% of the population. Each aspect of the disorder may vary in presentation, range, and severity, cumulating in a broad clinical spectrum. A genetic contribution to the etiology of ASD has been demonstrated and despite the high heterogeneity, there is evidence for the existence of clinical ASD subtypes. In genome-wide screening studies for de novo mutations underlying ASD and intellectual disability (ID), mutations in the ADNP gene are consistently reported among the most frequent. The ADNP gene plays a role in embryonic development, especially during the time of neuronal tube closure, and is involved in chromatin remodeling. The ambition of the AUTISYN consortium was to study a specific ASD form caused by mutations in the ADNP gene (Helsmoortel-Van der Aa syndrome) and the molecular mechanism underlying this disorder using several models.

The AUTISYN consortium has brought together a multi-national team that includes members who have been working on different aspects of this topic for many years. The consortium was coordinated by Frank Kooy from Belgium and included Illana Gozes from Israel, Pierre-Luc Germain from Italy and Christopher Pearson from Canada.

Group photo: AUTISYN consortium. Geert Vandeweyer, Michele Gabriele, Pierre-Luc Germain, Alessandro Vitriolo, Giuseppe Testa, Illana Gozes, Danilla Pallotta, Frank Kooy, Anke Van Dijck, Elisa Cappuyns, Christopher Pearson; © AUTISYN Consortium
Group photo: AUTISYN consortium. Geert Vandeweyer, Michele Gabriele, Pierre-Luc Germain, Alessandro Vitriolo, Giuseppe Testa, Illana Gozes, Danilla Pallotta, Frank Kooy, Anke Van Dijck, Elisa Cappuyns, Christopher Pearson; © AUTISYN Consortium
The ERA-Net Neuron provided us with a unique opportunity to join forces with collaborators all over Europe. In our case, we were able to assemble a consortium including 4 distinct disciplines. This way we were able to work on a single disorder, yet look at the underlying biology from completely different angles. This has catalyzed our research efforts and outcomes in a way that without ERA-Net networking would not have been possible.
Frank Kooy, AUTISYN coordinator:

The outcomes of the consortium include a collaborative paper, involving two of the consortium partners and published in the journal Biological Psychiatry, which describes the clinical details of a cohort of 78 individuals from 16 countries with a likely disruptive mutation in ADNP. The overview provided in the paper defines the full clinical spectrum of individuals with ADNP mutations - a specific autism subtype. The authors show that individuals with mutations in ADNP have many overlapping clinical features that are distinctive from those of other autism and/or ID syndromes, thus a novel subtype of ASD/ID is defined and evidence for a significant genotype-phenotype correlation is presented.

In addition to conducting excellent collaborative research and achieving significant outcomes, the AUTISYN Consortium sets a commendable example for effectively engaging with the patients' community. A patient community day, held on September 9, 2022, concluded a two-day conference organized by partners from the AUTISYN consortium at the University of Antwerp, Belgium. This event followed two days of intensive scientific discussions, where researchers delved into the intricate details of Helsmoortel-Van der Aa syndrome (HVDAS) and the genetic mutations in ADNP underlying it. The patient community day marked a pivotal moment in the dialogue between researchers, clinicians, and families affected by HVDAS. Presentations during this day highlighted the historical context of syndrome discovery, detailed clinical presentations, insights from animal and cellular models, and updates on ongoing clinical trials. Moreover, the panel discussion facilitated direct engagement between experts and patients, allowing for the exchange of invaluable perspectives and insights. Patient community days, such as this, play a vital role in fostering collaboration, empowering individuals and families with knowledge, and ensuring that research efforts remain grounded in the needs and experiences of those directly affected. They not only enhance scientific understanding but also reinforce the sense of community and support crucial for advancing research and improving patient outcomes.

Moreover, project AUTISYN's sustainability is underscored by its successful collaboration efforts, as demonstrated by the acquisition of funding for the ADNPinMED project in JTC2018. This initiative, focusing on exploring the pleiotropic effects of ADNP in mental disorders, reflects the consortium's ongoing commitment to advancing understanding in this field. While not all previous consortium partners are involved in this new project, its inception showcases the consortium's adaptability and capacity to foster new collaborations while building upon existing expertise. Additionally, the announcement of a second conference, in a format akin to the previously described one, scheduled for September 11-13, 2024, further emphasizes the consortium's sustained commitment to scientific exchange and community engagement, ensuring continued progress and dissemination of findings in the field of Helsmoortel-Van der Aa syndrome research.

For reference: Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A, Bernier R, Gozes I, Eichler EE, Romano C, Lindstrand A, Nordgren A; ADNP Consortium; Kvarnung M, Kleefstra T, de Vries BBA, Küry S, Rosenfeld JA, Meuwissen ME, Vandeweyer G, Kooy RF. Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP. Biol Psychiatry. 2019 Feb 15;85(4):287-297. doi: 10.1016/j.biopsych.2018.02.1173. Epub 2018 Mar 15. PMID: 29724491; PMCID: PMC6139063.