Dr. Claudio Peter D’Incal publishes new study in EBioMedicine (The Lancet series) on ADNP-related disease mechanisms
We are pleased to share a new publication by Dr. Claudio Peter D’Incal in EBioMedicine, a leading translational research journal from The Lancet Discovery Science portfolio (impact factor 11). The paper, entitled “An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice”, provides important new insights into the molecular pathology of Helsmoortel–Van der Aa syndrome (HVDAS), a rare neurodevelopmental disorder caused by pathogenic variants in the ADNP gene that was initially discovered at the Center of Medical Genetics in Antwerp, Belgium.
HVDAS is one of the more frequent monogenic causes of autism spectrum disorder and intellectual disability, yet the biological consequences of ADNP disruption remain incompletely understood. In this study, Dr. D’Incal and colleagues investigated the effects of a disease-relevant Adnp frameshift variant in a mouse model, focusing on how ADNP deficiency alters cellular pathways that are essential for brain development and behaviour. The work identifies a disruption of Wnt signalling, together with marked chromatin and cytoskeletal abnormalities, thereby linking ADNP dysfunction to molecular processes that are central to neuronal development, synaptic organisation and behavioural regulation. Importantly, the study also demonstrates that these alterations are associated with autism-related behavioural phenotypes, providing a mechanistic bridge between a pathogenic ADNP variant and the neurobehavioural manifestations observed in patients. By integrating molecular, cellular and behavioural analyses, this publication further strengthens our understanding of the pathways disrupted in ADNP syndrome and highlights potential entry points for future therapeutic intervention. The study forms part of our broader effort at the Centre of Medical Genetics Antwerp to unravel the pathophysiology of rare neurodevelopmental disorders and to translate mechanistic insights into improved diagnostics and treatment strategies.
Publication details
Author: Dr Claudio Peter D’Incal
Title:An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice
Journal:EBioMedicine
Impact factor: 11
Read the paper:
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00191-X/fulltext
